Genetic Variant NM_001136218.2:c.713A>G (chr1-15219694-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136218.2(TMEM51):c.713A>G(p.Gln238Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

TMEM51
NM_001136218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20932153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM51	NM_001136218.2 link	c.713A>G	p.Gln238Arg	missense_variant	Exon 4 of 4	ENST00000376008.3	NP_001129690.1	Q9NW97A0A024QZ97

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM51	ENST00000376008.3 link	c.713A>G	p.Gln238Arg	missense_variant	Exon 4 of 4	2	NM_001136218.2	ENSP00000365176.1		Q9NW97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248968

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000533

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000764

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.713A>G (p.Q238R) alteration is located in exon 4 (coding exon 2) of the TMEM51 gene. This alteration results from a A to G substitution at nucleotide position 713, causing the glutamine (Q) at amino acid position 238 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.62

T;.;.;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

M;M;M;M

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.099

Sift

Benign

0.033

D;D;D;D

Sift4G

Uncertain

0.056

T;T;T;T

Polyphen

0.16

B;B;B;B

Vest4

0.29

MVP

0.20

MPC

0.25

ClinPred

0.36

GERP RS

4.2

Varity_R

0.18

gMVP

0.54

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