Variant 5-73173472-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000296776.6(TMEM174):c.229G>A(p.Val77Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000935 in 1,614,202 control chromosomes in the GnomAD database, including 2 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 2 hom. )

Consequence

TMEM174
ENST00000296776.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

TMEM174 (HGNC:28187): (transmembrane protein 174) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM174 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007908672).

BP6

Variant 5-73173472-G-A is Benign according to our data. Variant chr5-73173472-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2300025.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM174	NM_153217.3 linkuse as main transcript	c.229G>A	p.Val77Ile	missense_variant	1/2	ENST00000296776.6	NP_694949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM174	ENST00000296776.6 linkuse as main transcript	c.229G>A	p.Val77Ile	missense_variant	1/2	1	NM_153217.3	ENSP00000296776	P1	Q8WUU8-1
TMEM174	ENST00000511737.1 linkuse as main transcript	n.181G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

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:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000717

AC:

180

AN:

251214

Hom.:

AF XY:

0.000670

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000958

AC:

1401

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000938

AC XY:

682

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152312

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000685

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.24

DEOGEN2

Benign

0.021

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.61

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.3

MutationTaster

Benign

0.99

PrimateAI

Benign

0.31

PROVEAN

Benign

0.64

REVEL

Benign

0.078

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MVP

0.030

MPC

0.019

ClinPred

0.0032

GERP RS

4.8

Varity_R

0.053

gMVP

0.22

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