Variant X-153982076-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000369982.5(TMEM187):c.14G>C(p.Trp5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,211,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 0.00013 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )

Consequence

TMEM187
ENST00000369982.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.686

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=0.017345697).

BP6

Variant X-153982076-G-C is Benign according to our data. Variant chrX-153982076-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2255178.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.14G>C	p.Trp5Ser	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.14G>C	p.Trp5Ser	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4	Q14656
TMEM187	ENST00000425274.1 linkuse as main transcript	c.14G>C	p.Trp5Ser	missense_variant	2/2	5		ENSP00000390108.1	C9JIP7
TMEM187	ENST00000431598.1 linkuse as main transcript	c.14G>C	p.Trp5Ser	missense_variant	2/2	3		ENSP00000412872.1	C9JV55

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

113711

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

35843

show subpopulations

Gnomad AFR

AF:

0.000478

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:

0.0000770

AC:

AN:

181915

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

66825

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.0000730

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:

0.00

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1098080

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363500

show subpopulations

Gnomad4 AFR exome

AF:

0.000417

Gnomad4 AMR exome

AF:

0.0000568

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:

0.00

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000132

AC:

AN:

113711

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

35843

show subpopulations

Gnomad4 AFR

AF:

0.000478

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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

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

Oct 12, 2021

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

0.074

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.43

DANN

Benign

0.59

DEOGEN2

Benign

0.00084

T;.;.

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.26

T;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.57

N;N;D

REVEL

Benign

0.036

Sift

Benign

0.90

T;T;.

Sift4G

Benign

0.44

T;T;D

Polyphen

0.0

B;.;.

Vest4

0.072

MVP

0.092

MPC

0.26

ClinPred

0.012

GERP RS

-2.3

Varity_R

0.074

gMVP

0.37

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