Variant 4-957834-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032326.4(TMEM175):c.853G>A(p.Val285Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000295 in 1,608,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

TMEM175
NM_032326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

TMEM175 (HGNC:28709): (transmembrane protein 175) Enables potassium ion leak channel activity. Involved in potassium ion transmembrane transport. Located in endosome and lysosome. Is integral component of endosome membrane and integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM175 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08742684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM175	NM_032326.4 linkuse as main transcript	c.853G>A	p.Val285Ile	missense_variant	11/11	ENST00000264771.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM175	ENST00000264771.9 linkuse as main transcript	c.853G>A	p.Val285Ile	missense_variant	11/11	1	NM_032326.4	P1	Q9BSA9-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000298

AC:

AN:

245142

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

132828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.000625

Gnomad EAS exome

AF:

0.000601

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000438

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.000300

AC:

437

AN:

1456114

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

221

AN XY:

723956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000583

Gnomad4 EAS exome

AF:

0.000631

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.0000577

Gnomad4 NFE exome

AF:

0.000328

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000249

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000369

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 26, 2023

The c.853G>A (p.V285I) alteration is located in exon 11 (coding exon 10) of the TMEM175 gene. This alteration results from a G to A substitution at nucleotide position 853, causing the valine (V) at amino acid position 285 to be replaced by an isoleucine (I). 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

0.093

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0056

T;T;.;.;T;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

T;T;.;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.087

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

L;.;.;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.020

N;N;N;N;N;.

REVEL

Benign

0.16

Sift

Benign

0.26

T;T;T;T;T;.

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.99

D;.;.;D;.;.

Vest4

0.19

MVP

0.14

MPC

0.15

ClinPred

0.092

GERP RS

4.0

Varity_R

0.12

gMVP

0.52

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