Variant 4-952440-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032326.4(TMEM175):c.452G>C(p.Gly151Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000711 in 1,588,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

TMEM175
NM_032326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37939218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM175	NM_032326.4 linkuse as main transcript	c.452G>C	p.Gly151Ala	missense_variant	7/11	ENST00000264771.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM175	ENST00000264771.9 linkuse as main transcript	c.452G>C	p.Gly151Ala	missense_variant	7/11	1	NM_032326.4	P1	Q9BSA9-1

Frequencies

GnomAD3 genomes

AF:

0.0000731

AC:

AN:

150518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000564

AC:

AN:

248332

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000107

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000709

AC:

102

AN:

1437714

Hom.:

Cov.:

AF XY:

0.0000630

AC XY:

AN XY:

714696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000460

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.0000872

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

AF:

0.0000730

AC:

AN:

150626

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73566

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000725

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000332

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

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 19, 2023

The c.452G>C (p.G151A) alteration is located in exon 7 (coding exon 6) of the TMEM175 gene. This alteration results from a G to C substitution at nucleotide position 452, causing the glycine (G) at amino acid position 151 to be replaced by an alanine (A). 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

0.36

BayesDel_addAF

Benign

-0.0093

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;.;T;.;.;.;T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.097

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D;D;.;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.5

M;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.4

N;D;N;D;N;N;N;.

REVEL

Uncertain

0.35

Sift

Benign

0.087

T;D;T;T;T;D;D;.

Sift4G

Benign

0.093

T;D;T;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;.;D;.

Vest4

0.72

MVP

0.33

MPC

0.69

ClinPred

0.42

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.37

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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