dbSNP rs767898181: FAM131C:p.Gly249Arg (chr1-16058535-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182623.3(FAM131C):c.745G>C(p.Gly249Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 48)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM131C
NM_182623.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.621

Variant links:

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

FAM131C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040532857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM131C	NM_182623.3 link	c.745G>C	p.Gly249Arg	missense_variant	Exon 7 of 7	ENST00000375662.5	NP_872429.2	Q96AQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM131C	ENST00000375662.5 link	c.745G>C	p.Gly249Arg	missense_variant	Exon 7 of 7	1	NM_182623.3	ENSP00000364814.4		Q96AQ9
FAM131C	ENST00000494078.1 link	n.819G>C		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000348

AC:

AN:

114868

Hom.:

AF XY:

0.0000331

AC XY:

AN XY:

60376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000548

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000190

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000153

AC:

AN:

1371606

Hom.:

Cov.:

AF XY:

0.0000133

AC XY:

AN XY:

675076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000320

Gnomad4 AMR exome

AF:

0.0000972

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000842

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000144

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.70

M_CAP

Benign

0.0093

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.6

REVEL

Benign

0.037

Sift

Benign

0.051

Sift4G

Benign

0.17

Polyphen

0.12

Vest4

0.065

MutPred

0.14

Gain of solvent accessibility (P = 0.019);

MVP

0.35

MPC

0.65

ClinPred

0.033

GERP RS

0.38

Varity_R

0.049

gMVP

0.20

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over