Variant 12-128415340-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001136103.3(TMEM132C):c.694G>A(p.Val232Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,582,168 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.012 ( 34 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030611455).

BP6

Variant 12-128415340-G-A is Benign according to our data. Variant chr12-128415340-G-A is described in ClinVar as [Benign]. Clinvar id is 776778.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1894/152192) while in subpopulation AFR AF= 0.0435 (1806/41500). AF 95% confidence interval is 0.0418. There are 34 homozygotes in gnomad4. There are 881 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM132C	NM_001136103.3 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/9	ENST00000435159.3
TMEM132C	NM_001387058.1 linkuse as main transcript	c.634G>A	p.Val212Met	missense_variant	2/9
TMEM132C	XM_047429886.1 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.694G>A	p.Val232Met	missense_variant	2/9	5	NM_001136103.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1881

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00281

AC:

558

AN:

198264

Hom.:

AF XY:

0.00221

AC XY:

236

AN XY:

106734

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000771

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000820

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00123

AC:

1763

AN:

1429976

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

750

AN XY:

707874

show subpopulations

Gnomad4 AFR exome

AF:

0.0438

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000607

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000575

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.0124

AC:

1894

AN:

152192

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

881

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.0146

ESP6500AA

AF:

0.0506

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.00304

AC:

366

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.66

REVEL

Benign

0.056

Sift

Benign

0.12

Sift4G

Benign

0.15

Polyphen

0.91

Vest4

0.24

MVP

0.043

MPC

0.18

ClinPred

0.010

GERP RS

1.7

Varity_R

0.041

gMVP

0.35

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