Variant rs34311866 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032326.4(TMEM175):c.1178T>C(p.Met393Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,603,214 control chromosomes in the GnomAD database, including 29,080 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2053 hom., cov: 34)

Exomes 𝑓: 0.19 ( 27027 hom. )

Consequence

TMEM175
NM_032326.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.29

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023782551).

BP6

Variant 4-958159-T-C is Benign according to our data. Variant chr4-958159-T-C is described in ClinVar as [Benign]. Clinvar id is 1246424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM175	NM_032326.4 linkuse as main transcript	c.1178T>C	p.Met393Thr	missense_variant	11/11	ENST00000264771.9	NP_115702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM175	ENST00000264771.9 linkuse as main transcript	c.1178T>C	p.Met393Thr	missense_variant	11/11	1	NM_032326.4	ENSP00000264771	P1	Q9BSA9-1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21549

AN:

152150

Hom.:

2055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.180

AC:

43259

AN:

240964

Hom.:

4867

AF XY:

0.194

AC XY:

25497

AN XY:

131664

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.0718

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.185

AC:

268511

AN:

1450946

Hom.:

27027

Cov.:

AF XY:

0.191

AC XY:

137971

AN XY:

722146

show subpopulations

Gnomad4 AFR exome

AF:

0.0277

Gnomad4 AMR exome

AF:

0.0751

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.141

AC:

21543

AN:

152268

Hom.:

2053

Cov.:

AF XY:

0.144

AC XY:

10707

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.264

Hom.:

5279

Bravo

AF:

0.122

TwinsUK

AF:

0.180

AC:

667

ALSPAC

AF:

0.173

AC:

667

ESP6500AA

AF:

0.0355

AC:

156

ESP6500EA

AF:

0.190

AC:

1629

ExAC

AF:

0.181

AC:

21957

Asia WGS

AF:

0.227

AC:

787

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 31658403, 31261387, 30389748) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.5

DANN

Benign

0.45

DEOGEN2

Benign

0.015

T;.;.;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.59

T;.;T;T

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

N;N;N;.

REVEL

Benign

0.15

Sift

Benign

0.032

D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.0

B;.;B;.

Vest4

0.038

MPC

0.18

ClinPred

0.0029

GERP RS

0.79

Varity_R

0.22

gMVP

0.75

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