Genetic Variant NM_001312909.2:c.140G>A (chr11-59151808-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001312909.2(FAM111A):c.140G>A(p.Gly47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FAM111A
NM_001312909.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330

Publications

0 publications found

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]

FAM111A links:

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

FAM111A-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0485543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312909.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM111A	NM_001312909.2	MANE Select	c.140G>A	p.Gly47Glu	missense	Exon 6 of 6	NP_001299838.1	Q96PZ2
FAM111A	NM_001142519.3		c.140G>A	p.Gly47Glu	missense	Exon 5 of 5	NP_001135991.1	Q96PZ2
FAM111A	NM_001142520.3		c.140G>A	p.Gly47Glu	missense	Exon 5 of 5	NP_001135992.1	Q96PZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM111A	ENST00000675163.1	MANE Select	c.140G>A	p.Gly47Glu	missense	Exon 6 of 6	ENSP00000501952.1	Q96PZ2
FAM111A	ENST00000531147.1	TSL:1	c.140G>A	p.Gly47Glu	missense	Exon 2 of 2	ENSP00000431631.1	Q96PZ2
FAM111A	ENST00000361723.7	TSL:2	c.140G>A	p.Gly47Glu	missense	Exon 4 of 4	ENSP00000355264.3	Q96PZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0063

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.39

M_CAP

Benign

0.019

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.033

PrimateAI

Benign

0.23

PROVEAN

Benign

1.0

REVEL

Benign

0.058

Sift

Benign

0.094

Sift4G

Benign

0.94

Polyphen

0.0050

Vest4

0.081

MutPred

0.14

Gain of solvent accessibility (P = 0.024)

MVP

0.32

MPC

0.023

ClinPred

0.046

GERP RS

-3.1

Varity_R

0.031

gMVP

0.048

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over