Variant 2-97760871-T-C 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_015348.2(TMEM131):c.4933A>G(p.Thr1645Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TMEM131
NM_015348.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

TMEM131 (HGNC:30366): (transmembrane protein 131) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM131 links:

TMEM131 (HGNC:):

TMEM131 links:

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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=0.044290215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM131	NM_015348.2 linkuse as main transcript	c.4933A>G	p.Thr1645Ala	missense_variant	37/41	ENST00000186436.10	NP_056163.1	Q92545

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM131	ENST00000186436.10 linkuse as main transcript	c.4933A>G	p.Thr1645Ala	missense_variant	37/41	5	NM_015348.2	ENSP00000186436.5	Q92545
TMEM131	ENST00000485245.2 linkuse as main transcript	n.4447A>G		non_coding_transcript_exon_variant	1/2	1
TMEM131	ENST00000465767.1 linkuse as main transcript	n.327A>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249230

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

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

Oct 16, 2024

The c.4933A>G (p.T1645A) alteration is located in exon 37 (coding exon 37) of the TMEM131 gene. This alteration results from a A to G substitution at nucleotide position 4933, causing the threonine (T) at amino acid position 1645 to be replaced by an alanine (A). 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

0.067

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

M_CAP

Benign

0.0027

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.4

REVEL

Benign

0.061

Sift

Benign

0.26

Sift4G

Benign

0.84

Polyphen

0.0010

Vest4

0.12

MutPred

0.20

Gain of helix (P = 0.0117);

MVP

0.043

MPC

0.19

ClinPred

0.12

GERP RS

3.0

Varity_R

0.033

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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