Variant X-153982108-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003492.3(TMEM187):c.46G>A(p.Gly16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,211,757 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 9 hem., cov: 25)

Exomes 𝑓: 0.000040 ( 0 hom. 13 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0087964535).

BP6

Variant X-153982108-G-A is Benign according to our data. Variant chrX-153982108-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2389721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TMEM187	ENST00000369982.5 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	2/2	1	NM_003492.3	P1
TMEM187	ENST00000425274.1 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	2/2	5
TMEM187	ENST00000431598.1 linkuse as main transcript	c.46G>A	p.Gly16Ser	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000291

AC:

AN:

113587

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

AN XY:

35721

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000277

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182022

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

66888

show subpopulations

Gnomad AFR exome

AF:

0.000841

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1098117

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

363529

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000237

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000290

AC:

AN:

113640

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

AN XY:

35784

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000278

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Apr 12, 2022

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

0.069

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.37

DANN

Benign

0.75

DEOGEN2

Benign

0.00060

T;.;.

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0088

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.96

N;N;N

REVEL

Benign

0.014

Sift

Benign

0.64

T;T;.

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.030

MVP

0.23

MPC

0.16

ClinPred

0.0073

GERP RS

-4.0

Varity_R

0.060

gMVP

0.18

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