Variant 12-128267416-G-A 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.14G>A(p.Gly5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,226,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

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=0.0060928166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132C	NM_001136103.3 linkuse as main transcript	c.14G>A	p.Gly5Asp	missense_variant	1/9	ENST00000435159.3	NP_001129575.2
TMEM132C	XM_047429886.1 linkuse as main transcript	c.14G>A	p.Gly5Asp	missense_variant	1/9		XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.14G>A	p.Gly5Asp	missense_variant	1/9	5	NM_001136103.3	ENSP00000410852	P1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

231

AN:

150260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000360

AC:

AN:

2774

Hom.:

AF XY:

0.000585

AC XY:

AN XY:

1708

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:

0.00250

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

140

AN:

1076386

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

514330

show subpopulations

Gnomad4 AFR exome

AF:

0.00457

Gnomad4 AMR exome

AF:

0.000507

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000358

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000654

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00154

AC:

232

AN:

150366

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

119

AN XY:

73430

show subpopulations

Gnomad4 AFR

AF:

0.00489

Gnomad4 AMR

AF:

0.00139

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00193

ExAC

AF:

0.00113

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

Jul 20, 2021

The c.14G>A (p.G5D) alteration is located in exon 1 (coding exon 1) of the TMEM132C gene. This alteration results from a G to A substitution at nucleotide position 14, causing the glycine (G) at amino acid position 5 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

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00043

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.52

REVEL

Benign

0.033

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Vest4

0.48

MVP

0.043

MPC

0.12

ClinPred

0.27

GERP RS

1.8

Varity_R

0.21

gMVP

0.37

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