Variant 1-15219723-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.742G>A(p.Asp248Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

TMEM51
NM_001136218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.759

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:

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=0.028413683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM51	NM_001136218.2 linkuse as main transcript	c.742G>A	p.Asp248Asn	missense_variant	4/4	ENST00000376008.3	NP_001129690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM51	ENST00000376008.3 linkuse as main transcript	c.742G>A	p.Asp248Asn	missense_variant	4/4	2	NM_001136218.2	ENSP00000365176	P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000129

AC:

AN:

247632

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

134922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.000804

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000536

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000965

AC:

141

AN:

1460838

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

Jun 11, 2024

The c.742G>A (p.D248N) 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 742, causing the aspartic acid (D) at amino acid position 248 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

0.070

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;T;T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.70

T;.;.;.

M_CAP

Benign

0.0061

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.061

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.14

MVP

0.082

MPC

0.18

ClinPred

0.021

GERP RS

1.3

Varity_R

0.042

gMVP

0.27

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