Variant X-153982397-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_003492.3(TMEM187):c.335C>T(p.Ala112Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000234 in 1,198,226 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.000023 ( 0 hom. 8 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM187	NM_003492.3 linkuse as main transcript	c.335C>T	p.Ala112Val	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.335C>T	p.Ala112Val	missense_variant	2/2	1	NM_003492.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

113603

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

35757

show subpopulations

Gnomad AFR

AF:

0.0000638

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000230

AC:

AN:

1084623

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

355247

show subpopulations

Gnomad4 AFR exome

AF:

0.000532

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000336

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000131

GnomAD4 genome

AF:

0.0000264

AC:

AN:

113603

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

35757

show subpopulations

Gnomad4 AFR

AF:

0.0000638

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:

0.0000187

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Mar 29, 2022

The c.335C>T (p.A112V) alteration is located in exon 2 (coding exon 1) of the TMEM187 gene. This alteration results from a C to T substitution at nucleotide position 335, causing the alanine (A) at amino acid position 112 to be replaced by a valine (V). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.091

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.27

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.62

MutPred

0.31

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.26

MPC

0.37

ClinPred

0.97

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.76

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