Variant 4-957831-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032326.4(TMEM175):c.850A>G(p.Asn284Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000554 in 1,606,482 control chromosomes in the GnomAD database, including 5 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00050 ( 4 hom. )

Consequence

TMEM175
NM_032326.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.56

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008975238).

BP6

Variant 4-957831-A-G is Benign according to our data. Variant chr4-957831-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3067237.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM175	NM_032326.4 linkuse as main transcript	c.850A>G	p.Asn284Asp	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.850A>G	p.Asn284Asp	missense_variant	11/11	1	NM_032326.4	P1	Q9BSA9-1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000918

AC:

224

AN:

243940

Hom.:

AF XY:

0.000878

AC XY:

116

AN XY:

132166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00633

Gnomad NFE exome

AF:

0.000780

Gnomad OTH exome

AF:

0.000502

GnomAD4 exome

AF:

0.000501

AC:

728

AN:

1454138

Hom.:

Cov.:

AF XY:

0.000500

AC XY:

361

AN XY:

722700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.0000781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00610

Gnomad4 NFE exome

AF:

0.000349

Gnomad4 OTH exome

AF:

0.000316

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152344

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00810

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000668

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000733

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

TMEM175: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;.;.;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D;.;D;D;D

M_CAP

Benign

0.069

MetaRNN

Benign

0.0090

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.1

L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.5

N;N;N;N;N;.

REVEL

Benign

0.20

Sift

Benign

0.12

T;T;T;T;T;.

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.97

D;.;.;D;.;.

Vest4

0.60

MVP

0.24

MPC

0.39

ClinPred

0.11

GERP RS

4.8

Varity_R

0.59

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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