Variant 12-128415446-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136103.3(TMEM132C):c.800A>G(p.Gln267Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000452 in 1,551,708 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0477601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM132C	NM_001136103.3 linkuse as main transcript	c.800A>G	p.Gln267Arg	missense_variant	2/9	ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1 linkuse as main transcript	c.740A>G	p.Gln247Arg	missense_variant	2/9		NP_001373987.1
TMEM132C	XM_047429886.1 linkuse as main transcript	c.800A>G	p.Gln267Arg	missense_variant	2/9		XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.800A>G	p.Gln267Arg	missense_variant	2/9	5	NM_001136103.3	ENSP00000410852	P1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000208

AC:

AN:

153954

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

81620

show subpopulations

Gnomad AFR exome

AF:

0.000126

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:

0.000471

Gnomad OTH exome

AF:

0.000692

GnomAD4 exome

AF:

0.000480

AC:

672

AN:

1399440

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

336

AN XY:

690218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000560

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:

0.000603

Gnomad4 OTH exome

AF:

0.000327

GnomAD4 genome

AF:

0.000190

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

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

Jan 05, 2022

The c.800A>G (p.Q267R) alteration is located in exon 2 (coding exon 2) of the TMEM132C gene. This alteration results from a A to G substitution at nucleotide position 800, causing the glutamine (Q) at amino acid position 267 to be replaced by an arginine (R). 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

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.68

M_CAP

Benign

0.0056

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.93

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.3

REVEL

Benign

0.044

Sift

Benign

0.76

Sift4G

Benign

0.95

Polyphen

0.074

Vest4

0.079

MVP

0.068

MPC

0.11

ClinPred

0.041

GERP RS

3.9

Varity_R

0.13

gMVP

0.47

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