Variant X-153982090-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003492.3(TMEM187):c.28G>A(p.Val10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000908 in 1,211,835 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

TMEM187 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027090818).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.28G>A	p.Val10Met	missense_variant	2/2	ENST00000369982.5	NP_003483.1	Q14656

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM187	ENST00000369982.5 linkuse as main transcript	c.28G>A	p.Val10Met	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4	Q14656
TMEM187	ENST00000425274.1 linkuse as main transcript	c.28G>A	p.Val10Met	missense_variant	2/2	5		ENSP00000390108.1	C9JIP7
TMEM187	ENST00000431598.1 linkuse as main transcript	c.28G>A	p.Val10Met	missense_variant	2/2	3		ENSP00000412872.1	C9JV55

Frequencies

GnomAD3 genomes

AF:

0.0000176

AC:

AN:

113689

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35807

show subpopulations

Gnomad AFR

AF:

0.0000637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000275

AC:

AN:

182085

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

66941

show subpopulations

Gnomad AFR exome

AF:

0.000153

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:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000820

AC:

AN:

1098094

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000475

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000176

AC:

AN:

113741

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35869

show subpopulations

Gnomad4 AFR

AF:

0.0000636

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.039

DANN

Benign

0.72

DEOGEN2

Benign

0.0027

T;.;.

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.31

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.28

T;T;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0070

B;.;.

Vest4

0.046

MVP

0.18

MPC

0.16

ClinPred

0.024

GERP RS

-3.9

Varity_R

0.038

gMVP

0.073

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