NM_001312909.2:c.1012A>G

Variant names:

• chr11-59152680-A-G
• rs587777014
• NM_001312909.2:c.1012A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001312909.2(FAM111A):​c.1012A>G​(p.Thr338Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T338R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM111A NM_001312909.2 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.71
• Publications: 7 publications found

Genes affected

FAM111A (HGNC:24725): (FAM111 trypsin like peptidase A) The protein encoded by this gene is cell-cycle regulated, and has nuclear localization. The C-terminal half of the protein shares homology with trypsin-like peptidases and it contains a PCNA-interacting peptide (PIP) box, that is necessary for its co-localization with proliferating cell nuclear antigen (PCNA). Reduced expression of this gene resulted in DNA replication defects, consistent with the demonstrated role for this gene in Simian Virus 40 (SV40) viral replication. Mutations in this gene have been associated with Kenny-Caffey syndrome (KCS) type 2 and the more severe osteocraniostenosis (OCS, also known as Gracile Bone Dysplasia), both characterized by short stature, hypoparathyroidism, bone development abnormalities, and hypocalcemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

FAM111A-DT (HGNC:53752): (FAM111A divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-59152680-A-G is Pathogenic according to our data. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-59152680-A-G is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 56814.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM111A	NM_001312909.2	c.1012A>G	p.Thr338Ala	missense_variant	Exon 6 of 6	ENST00000675163.1	NP_001299838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM111A	ENST00000675163.1	c.1012A>G	p.Thr338Ala	missense_variant	Exon 6 of 6		NM_001312909.2	ENSP00000501952.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000653 Hom.: 0

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Osteocraniostenosis Pathogenic:2

Jun 27, 2013

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 06, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.39	.;T;.;.;.
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L;L;L;L
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Benign	0.098
Sift	Uncertain	0.0090	D;D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D
Polyphen		0.39	B;B;B;B;B
Vest4		0.61
MutPred		0.62		Loss of disorder (P = 0.1098);Loss of disorder (P = 0.1098);Loss of disorder (P = 0.1098);Loss of disorder (P = 0.1098);Loss of disorder (P = 0.1098);
MVP		0.68
MPC		0.026
ClinPred		0.68	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.37
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777014; hg19: chr11-58920153;