Variant X-153982475-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003492.3(TMEM187):c.413G>A(p.Arg138Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,202,302 control chromosomes in the GnomAD database, including 64 homozygotes. There are 908 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 37 hom., 449 hem., cov: 26)

Exomes 𝑓: 0.0016 ( 27 hom. 459 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0660

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015996099).

BP6

Variant X-153982475-G-A is Benign according to our data. Variant chrX-153982475-G-A is described in ClinVar as [Benign]. Clinvar id is 711792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (1631/113489) while in subpopulation AFR AF= 0.0493 (1546/31361). AF 95% confidence interval is 0.0473. There are 37 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	2/2	ENST00000369982.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM187	ENST00000369982.5 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	2/2	1	NM_003492.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

1630

AN:

113435

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

451

AN XY:

35571

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00555

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.00784

GnomAD3 exomes

AF:

0.00490

AC:

819

AN:

167271

Hom.:

AF XY:

0.00340

AC XY:

193

AN XY:

56691

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.00158

AC:

1717

AN:

1088813

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

459

AN XY:

358221

show subpopulations

Gnomad4 AFR exome

AF:

0.0480

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000667

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000191

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.0144

AC:

1631

AN:

113489

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

449

AN XY:

35635

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.00554

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000225

Gnomad4 OTH

AF:

0.00774

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.0170

ESP6500AA

AF:

0.0519

AC:

199

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00493

AC:

598

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.17

DANN

Benign

0.86

DEOGEN2

Benign

0.0014

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.10

REVEL

Benign

0.0030

Sift

Benign

0.33

Sift4G

Benign

0.47

Polyphen

0.010

Vest4

0.023

MVP

0.12

MPC

0.18

ClinPred

0.0030

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.30

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