Variant 7-150802272-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018487.3(TMEM176A):c.232C>T(p.Arg78Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

TMEM176A
NM_018487.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.546

Variant links:

Genes affected

TMEM176A (HGNC:24930): (transmembrane protein 176A) Predicted to be involved in negative regulation of dendritic cell differentiation. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM176A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1756998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM176A	NM_018487.3 linkuse as main transcript	c.232C>T	p.Arg78Cys	missense_variant	3/7	ENST00000004103.8	NP_060957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM176A	ENST00000004103.8 linkuse as main transcript	c.232C>T	p.Arg78Cys	missense_variant	3/7	1	NM_018487.3	ENSP00000004103	P1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251456

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000540

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000656

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151562

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Sep 23, 2023

The c.232C>T (p.R78C) alteration is located in exon 3 (coding exon 2) of the TMEM176A gene. This alteration results from a C to T substitution at nucleotide position 232, causing the arginine (R) at amino acid position 78 to be replaced by a cysteine (C). 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

Benign

0.094

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

DANN

Benign

0.70

DEOGEN2

Benign

0.0034

T;T;.;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.28

.;T;.;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.14

N;N;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.28

N;N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.20

MutPred

0.71

Loss of catalytic residue at R78 (P = 0.102);Loss of catalytic residue at R78 (P = 0.102);.;.;.;

MVP

0.12

MPC

0.46

ClinPred

0.027

GERP RS

-8.9

Varity_R

0.047

gMVP

0.12

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