Variant chr1-16058636-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182623.3(FAM131C):c.644G>T(p.Ser215Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,580,524 control chromosomes in the GnomAD database, including 5,151 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.22 ( 627 hom., cov: 44)

Exomes 𝑓: 0.20 ( 4524 hom. )

Consequence

FAM131C
NM_182623.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.457

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005001545).

BP6

Variant 1-16058636-C-A is Benign according to our data. Variant chr1-16058636-C-A is described in ClinVar as [Benign]. Clinvar id is 1249070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131C	NM_182623.3 link	c.644G>T	p.Ser215Ile	missense_variant	7/7	ENST00000375662.5	NP_872429.2	Q96AQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131C	ENST00000375662.5 link	c.644G>T	p.Ser215Ile	missense_variant	7/7	1	NM_182623.3	ENSP00000364814.4		Q96AQ9
FAM131C	ENST00000494078.1 link	n.718G>T		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

32800

AN:

148348

Hom.:

628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.00134

Gnomad SAS

AF:

0.0977

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.170

AC:

37416

AN:

219784

Hom.:

470

AF XY:

0.169

AC XY:

20029

AN XY:

118524

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.0929

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.000427

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.198

AC:

283584

AN:

1432054

Hom.:

4524

Cov.:

103

AF XY:

0.195

AC XY:

138559

AN XY:

710232

show subpopulations

Gnomad4 AFR exome

AF:

0.345

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.000588

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.241

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.221

AC:

32838

AN:

148470

Hom.:

627

Cov.:

AF XY:

0.217

AC XY:

15744

AN XY:

72596

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0975

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.218

Hom.:

248

ExAC

AF:

0.152

AC:

18296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 03, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.97

REVEL

Benign

0.038

Sift

Uncertain

0.012

Sift4G

Benign

0.20

Polyphen

0.078

Vest4

0.045

MPC

0.57

ClinPred

0.0062

GERP RS

3.5

Varity_R

0.12

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over