Variant chr12-129074541-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_133448.3(TMEM132D):c.2634G>T(p.Leu878Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 1,613,982 control chromosomes in the GnomAD database, including 1,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.057 ( 424 hom., cov: 32)

Exomes 𝑓: 0.031 ( 990 hom. )

Consequence

TMEM132D
NM_133448.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.354

Variant links:

Genes affected

TMEM132D (HGNC:29411): (transmembrane protein 132D)

TMEM132D links:

LOC124903086 (HGNC:):

LOC124903086 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018612444).

BP6

Variant 12-129074541-C-A is Benign according to our data. Variant chr12-129074541-C-A is described in ClinVar as [Benign]. Clinvar id is 3059245.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3 linkuse as main transcript	c.2634G>T	p.Leu878Phe	missense_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1 linkuse as main transcript	n.87-365C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7 linkuse as main transcript	c.2634G>T	p.Leu878Phe	missense_variant	9/9	1	NM_133448.3	P1	Q14C87-1
TMEM132D	ENST00000389441.8 linkuse as main transcript	c.1248G>T	p.Leu416Phe	missense_variant	4/4	1			Q14C87-2

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8670

AN:

151978

Hom.:

422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0282

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0296

AC:

7432

AN:

251474

Hom.:

264

AF XY:

0.0268

AC XY:

3640

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.0310

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0306

AC:

44744

AN:

1461886

Hom.:

990

Cov.:

AF XY:

0.0294

AC XY:

21367

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.00532

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.00627

Gnomad4 FIN exome

AF:

0.0318

Gnomad4 NFE exome

AF:

0.0313

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.0571

AC:

8684

AN:

152096

Hom.:

424

Cov.:

AF XY:

0.0559

AC XY:

4154

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0282

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0324

Hom.:

301

Bravo

AF:

0.0607

TwinsUK

AF:

0.0299

AC:

111

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.124

AC:

548

ESP6500EA

AF:

0.0297

AC:

255

ExAC

AF:

0.0326

AC:

3955

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0276

EpiControl

AF:

0.0271

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TMEM132D-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

DANN

Benign

0.86

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.032

Sift

Benign

0.25

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0090

B;B

Vest4

0.011

MutPred

0.19

.;Gain of catalytic residue at D874 (P = 0.0466);

MPC

0.26

ClinPred

0.0023

GERP RS

-1.8

Varity_R

0.063

gMVP

0.19

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