11-59148935-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001312909.2(FAM111A):​c.63C>T​(p.Ile21Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,612,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I21I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FAM111A
NM_001312909.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.51
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant 11-59148935-C-T is Benign according to our data. Variant chr11-59148935-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779147.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM111ANM_001312909.2 linkc.63C>T p.Ile21Ile synonymous_variant Exon 5 of 6 ENST00000675163.1 NP_001299838.1 Q96PZ2A0A024R4Z3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM111AENST00000675163.1 linkc.63C>T p.Ile21Ile synonymous_variant Exon 5 of 6 NM_001312909.2 ENSP00000501952.1 Q96PZ2

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
42
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00778
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000482
AC:
121
AN:
251086
Hom.:
0
AF XY:
0.000494
AC XY:
67
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00113
Gnomad ASJ exome
AF:
0.00675
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000969
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000218
AC:
319
AN:
1460474
Hom.:
0
Cov.:
29
AF XY:
0.000222
AC XY:
161
AN XY:
726632
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00727
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.000514
GnomAD4 genome
AF:
0.000276
AC:
42
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000648
Hom.:
0
Bravo
AF:
0.000404
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FAM111A-related disorder Benign:1
Jun 18, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Jan 12, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.30
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.21
Position offset: 18

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147786828; hg19: chr11-58916408; COSMIC: COSV64655513; API