Variant 12-129074518-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_133448.3(TMEM132D):c.2657C>A(p.Thr886Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000461 in 1,614,098 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 8 hom. )

Consequence

TMEM132D
NM_133448.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.58

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058588088).

BP6

Variant 12-129074518-G-T is Benign according to our data. Variant chr12-129074518-G-T is described in ClinVar as [Benign]. Clinvar id is 3056991.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3 linkuse as main transcript	c.2657C>A	p.Thr886Asn	missense_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1 linkuse as main transcript	n.87-388G>T		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.2657C>A	p.Thr886Asn	missense_variant	9/9	1	NM_133448.3	P1	Q14C87-1
TMEM132D	ENST00000389441.8 linkuse as main transcript	c.1271C>A	p.Thr424Asn	missense_variant	4/4	1			Q14C87-2

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0155

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00114

AC:

286

AN:

251476

Hom.:

AF XY:

0.00107

AC XY:

145

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0134

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000446

AC:

652

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

340

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000604

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0155

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000996

Hom.:

Bravo

AF:

0.000808

ExAC

AF:

0.00102

AC:

124

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Feb 20, 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

0.091

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.31

B;D

Vest4

0.048

MVP

0.20

MPC

0.46

ClinPred

0.13

GERP RS

4.2

Varity_R

0.43

gMVP

0.46

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