Variant chr12-128415103-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001136103.3(TMEM132C):c.457A>G(p.Ile153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,608,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

TMEM132C (HGNC:25436): (transmembrane protein 132C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM132C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02330327).

BP6

Variant 12-128415103-A-G is Benign according to our data. Variant chr12-128415103-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2493279.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM132C	NM_001136103.3 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	2/9	ENST00000435159.3
TMEM132C	NM_001387058.1 linkuse as main transcript	c.397A>G	p.Ile133Val	missense_variant	2/9
TMEM132C	XM_047429886.1 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	2/9	5	NM_001136103.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

241854

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000737

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1456774

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

724240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000412

AC:

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

Mar 02, 2023

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

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0010

DANN

Benign

0.17

DEOGEN2

Benign

0.00076

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.68

M_CAP

Benign

0.0086

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.080

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.026

Vest4

0.017

MVP

0.043

MPC

0.077

ClinPred

0.019

GERP RS

-9.9

Varity_R

0.014

gMVP

0.20

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