Variant chr12-128414823-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001136103.3(TMEM132C):c.177G>T(p.Glu59Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,545,910 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.479

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018446356).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM132C	NM_001136103.3 linkuse as main transcript	c.177G>T	p.Glu59Asp	missense_variant	2/9	ENST00000435159.3
TMEM132C	NM_001387058.1 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/9
TMEM132C	XM_047429886.1 linkuse as main transcript	c.177G>T	p.Glu59Asp	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.177G>T	p.Glu59Asp	missense_variant	2/9	5	NM_001136103.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000233

AC:

AN:

150474

Hom.:

AF XY:

0.000212

AC XY:

AN XY:

80148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000486

Gnomad ASJ exome

AF:

0.000942

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000146

AC:

203

AN:

1393812

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

110

AN XY:

687704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.000420

Gnomad4 ASJ exome

AF:

0.000993

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.0000457

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000190

GnomAD4 genome

AF:

0.000178

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00157

AC:

ExAC

AF:

0.000124

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

Dec 14, 2023

The c.177G>T (p.E59D) alteration is located in exon 2 (coding exon 2) of the TMEM132C gene. This alteration results from a G to T substitution at nucleotide position 177, causing the glutamic acid (E) at amino acid position 59 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.6

DANN

Benign

0.55

DEOGEN2

Benign

0.00084

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.78

M_CAP

Benign

0.0091

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.51

MutationTaster

Benign

0.99

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.060

REVEL

Benign

0.078

Sift

Benign

0.97

Sift4G

Benign

0.97

Vest4

0.061

MutPred

0.34

Gain of sheet (P = 0.1208);

MVP

0.082

MPC

0.086

ClinPred

0.022

GERP RS

-3.5

Varity_R

0.063

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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