Variant X-153982528-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003492.3(TMEM187):c.466G>A(p.Ala156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,205,606 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 12 hem., cov: 25)

Exomes 𝑓: 0.000032 ( 0 hom. 8 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.44

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015549213).

BP6

Variant X-153982528-G-A is Benign according to our data. Variant chrX-153982528-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 724521.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.466G>A	p.Ala156Thr	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.466G>A	p.Ala156Thr	missense_variant	2/2	1	NM_003492.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000291

AC:

AN:

113365

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

35509

show subpopulations

Gnomad AFR

AF:

0.00106

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:

0.000126

AC:

AN:

173942

Hom.:

AF XY:

0.000115

AC XY:

AN XY:

60976

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000744

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:

0.000229

GnomAD4 exome

AF:

0.0000320

AC:

AN:

1092241

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

360305

show subpopulations

Gnomad4 AFR exome

AF:

0.000872

Gnomad4 AMR exome

AF:

0.0000857

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000291

AC:

AN:

113365

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

35509

show subpopulations

Gnomad4 AFR

AF:

0.00106

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:

0.0000407

Hom.:

Bravo

AF:

0.000385

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.466G>A (p.A156T) 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 466, causing the alanine (A) at amino acid position 156 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.2

DANN

Benign

0.95

DEOGEN2

Benign

0.0040

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.61

M_CAP

Benign

0.013

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.70

REVEL

Benign

0.028

Sift

Benign

0.37

Sift4G

Benign

0.45

Polyphen

0.014

Vest4

0.084

MVP

0.30

MPC

0.16

ClinPred

0.0076

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.41

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