Variant X-153982441-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.379G>A(p.Val127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,201,651 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.000026 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.355

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=0.06009072).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.379G>A	p.Val127Met	missense_variant	2/2	ENST00000369982.5	NP_003483.1	Q14656

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM187	ENST00000369982.5 linkuse as main transcript	c.379G>A	p.Val127Met	missense_variant	2/2	1	NM_003492.3	ENSP00000358999.4		Q14656

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

113730

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35848

show subpopulations

Gnomad AFR

AF:

0.0000955

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:

0.0000182

AC:

AN:

165008

Hom.:

AF XY:

0.00

AC XY:

AN XY:

55152

show subpopulations

Gnomad AFR exome

AF:

0.0000818

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:

0.0000133

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1087921

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

358015

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000578

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:

0.00000952

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000264

AC:

AN:

113730

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35848

show subpopulations

Gnomad4 AFR

AF:

0.0000955

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:

0.0000340

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.379G>A (p.V127M) alteration is located in exon 2 (coding exon 1) of the TMEM187 gene. This alteration results from a G to A substitution at nucleotide position 379, causing the valine (V) at amino acid position 127 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

DANN

Benign

0.89

DEOGEN2

Benign

0.0094

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.59

M_CAP

Benign

0.0046

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.0

REVEL

Benign

0.053

Sift

Benign

0.083

Sift4G

Benign

0.10

Polyphen

0.39

Vest4

0.086

MVP

0.26

MPC

0.23

ClinPred

0.028

GERP RS

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.070

gMVP

0.46

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