Variant chr12-129209529-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_133448.3(TMEM132D):c.1434C>T(p.Asp478Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,593,068 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 8 hom. )

Consequence

TMEM132D
NM_133448.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.660

Variant links:

Genes affected

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

TMEM132D links:

TMEM132D-AS2 (HGNC:):

TMEM132D-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-129209529-G-A is Benign according to our data. Variant chr12-129209529-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.66 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132D	NM_133448.3 linkuse as main transcript	c.1434C>T	p.Asp478Asp	synonymous_variant	5/9	ENST00000422113.7	NP_597705.2
TMEM132D-AS2	NR_110058.1 linkuse as main transcript	n.354-29G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7 linkuse as main transcript	c.1434C>T	p.Asp478Asp	synonymous_variant	5/9	1	NM_133448.3	ENSP00000408581.2		Q14C87-1
TMEM132D-AS2	ENST00000542578.1 linkuse as main transcript	n.354-29G>A		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

227

AN:

132282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000881

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000303

Gnomad ASJ

AF:

0.000327

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000526

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00132

AC:

330

AN:

250808

Hom.:

AF XY:

0.00128

AC XY:

173

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00254

AC:

3707

AN:

1460658

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1731

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00322

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00171

AC:

227

AN:

132410

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

102

AN XY:

64854

show subpopulations

Gnomad4 AFR

AF:

0.000878

Gnomad4 AMR

AF:

0.000302

Gnomad4 ASJ

AF:

0.000327

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000526

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00196

Hom.:

Bravo

AF:

0.00138

EpiCase

AF:

0.00213

EpiControl

AF:

0.00220

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.8

DANN

Benign

0.88

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