Variant 1-15219738-G-A 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_001136218.2(TMEM51):c.757G>A(p.Asp253Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,612,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

TMEM51
NM_001136218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

TMEM51 (HGNC:25488): (transmembrane protein 51) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM51 links:

TMEM51 (HGNC:):

TMEM51 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=0.02832207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM51	NM_001136218.2 linkuse as main transcript	c.757G>A	p.Asp253Asn	missense_variant	4/4	ENST00000376008.3	NP_001129690.1	Q9NW97A0A024QZ97

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM51	ENST00000376008.3 linkuse as main transcript	c.757G>A	p.Asp253Asn	missense_variant	4/4	2	NM_001136218.2	ENSP00000365176.1		Q9NW97

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.000382

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000268

AC:

AN:

246252

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

134334

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000280

Gnomad NFE exome

AF:

0.000423

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.000344

AC:

502

AN:

1460074

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

251

AN XY:

726182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000152

Gnomad4 NFE exome

AF:

0.000404

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000289

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000399

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000712

AC:

ExAC

AF:

0.000314

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000712

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

Jul 13, 2021

The c.757G>A (p.D253N) alteration is located in exon 4 (coding exon 2) of the TMEM51 gene. This alteration results from a G to A substitution at nucleotide position 757, causing the aspartic acid (D) at amino acid position 253 to be replaced by an asparagine (N). 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

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

T;T;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.66

T;.;.;.

M_CAP

Benign

0.0090

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;N;N;N

MutationTaster

Benign

0.74

N;N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.090

N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.90

T;T;T;T

Polyphen

0.19

B;B;B;B

Vest4

0.23

MVP

0.068

MPC

0.19

ClinPred

0.024

GERP RS

4.4

Varity_R

0.037

gMVP

0.34

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