Variant X-153982159-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 NM_003492.3(TMEM187):c.97G>C(p.Val33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,211,711 control chromosomes in the GnomAD database, including 1 homozygotes. There are 673 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., 51 hem., cov: 25)

Exomes 𝑓: 0.0018 ( 0 hom. 622 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.318

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=0.0135162175).

BP6

Variant X-153982159-G-C is Benign according to our data. Variant chrX-153982159-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 711110.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153982159-G-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.97G>C	p.Val33Leu	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.97G>C	p.Val33Leu	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4	Q14656
TMEM187	ENST00000425274.1 linkuse as main transcript	c.97G>C	p.Val33Leu	missense_variant	2/2	5		ENSP00000390108.1	C9JIP7
TMEM187	ENST00000431598.1 linkuse as main transcript	c.97G>C	p.Val33Leu	missense_variant, splice_region_variant	2/2	3		ENSP00000412872.1	C9JV55

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

135

AN:

113523

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

35657

show subpopulations

Gnomad AFR

AF:

0.000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000462

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00299

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.00130

GnomAD3 exomes

AF:

0.00102

AC:

185

AN:

181782

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

66796

show subpopulations

Gnomad AFR exome

AF:

0.000305

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00244

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.00180

AC:

1973

AN:

1098135

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

622

AN XY:

363545

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00220

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00119

AC:

135

AN:

113576

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

35720

show subpopulations

Gnomad4 AFR

AF:

0.000318

Gnomad4 AMR

AF:

0.000461

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00299

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.00129

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.000960

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.00121

AC:

147

EpiCase

AF:

0.00147

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.6

DANN

Benign

0.90

DEOGEN2

Benign

0.041

T;.;.

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

N;N;D

REVEL

Benign

0.10

Sift

Benign

0.041

D;D;.

Sift4G

Benign

0.075

T;D;D

Polyphen

0.58

P;.;.

Vest4

0.35

MutPred

0.24

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.12

MPC

0.30

ClinPred

0.0077

GERP RS

-0.96

Varity_R

0.12

gMVP

0.24

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