Variant 3-184344876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144635.5(FAM131A):c.1007C>T(p.Thr336Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,610,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

FAM131A
NM_144635.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.73

Variant links:

Genes affected

FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

FAM131A 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=0.00475353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131A	NM_144635.5 linkuse as main transcript	c.1007C>T	p.Thr336Met	missense_variant	6/6	ENST00000383847.7	NP_653236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131A	ENST00000383847.7 linkuse as main transcript	c.1007C>T	p.Thr336Met	missense_variant	6/6	2	NM_144635.5	ENSP00000373360	A1	Q6UXB0-3

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000383

AC:

AN:

245142

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

133538

show subpopulations

Gnomad AFR exome

AF:

0.000831

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00261

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000527

Gnomad NFE exome

AF:

0.000395

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000370

AC:

540

AN:

1458542

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

278

AN XY:

725774

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152334

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000584

Hom.:

Bravo

AF:

0.000808

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000890

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2022

The c.1007C>T (p.T336M) alteration is located in exon 6 (coding exon 6) of the FAM131A gene. This alteration results from a C to T substitution at nucleotide position 1007, causing the threonine (T) at amino acid position 336 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0070

DANN

Benign

0.90

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.25

.;.;T;T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0048

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.20

N;N;.;N;N;N

REVEL

Benign

0.0050

Sift

Benign

0.74

T;T;.;T;T;T

Sift4G

Benign

0.11

T;T;.;T;T;T

Vest4

0.10

MVP

0.085

MPC

0.41

ClinPred

0.0069

GERP RS

-4.6

Varity_R

0.053

gMVP

0.24

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over