Variant 4-952438-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_032326.4(TMEM175):c.450T>C(p.Ile150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,601,740 control chromosomes in the GnomAD database, including 291,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 28958 hom., cov: 27)

Exomes 𝑓: 0.60 ( 262741 hom. )

Consequence

TMEM175
NM_032326.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.375

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-952438-T-C is Benign according to our data. Variant chr4-952438-T-C is described in ClinVar as [Benign]. Clinvar id is 3060771.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.375 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM175	NM_032326.4 linkuse as main transcript	c.450T>C	p.Ile150=	synonymous_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.450T>C	p.Ile150=	synonymous_variant	7/11	1	NM_032326.4	P1	Q9BSA9-1

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

92118

AN:

148352

Hom.:

28932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.550

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.735

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.619

GnomAD3 exomes

AF:

0.591

AC:

146790

AN:

248396

Hom.:

44546

AF XY:

0.596

AC XY:

80116

AN XY:

134480

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.734

Gnomad SAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.523

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.599

AC:

870649

AN:

1453282

Hom.:

262741

Cov.:

AF XY:

0.601

AC XY:

434329

AN XY:

723216

show subpopulations

Gnomad4 AFR exome

AF:

0.729

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.597

Gnomad4 EAS exome

AF:

0.657

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.527

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.615

GnomAD4 genome

AF:

0.621

AC:

92181

AN:

148458

Hom.:

28958

Cov.:

AF XY:

0.614

AC XY:

44423

AN XY:

72294

show subpopulations

Gnomad4 AFR

AF:

0.720

Gnomad4 AMR

AF:

0.520

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.703

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.622

Alfa

AF:

0.576

Hom.:

7292

Bravo

AF:

0.631

EpiCase

AF:

0.601

EpiControl

AF:

0.608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TMEM175-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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