12-129074004-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_133448.3(TMEM132D):c.3171C>T(p.Asp1057=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,613,952 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (4 hom.)
• Consequence: TMEM132D NM_133448.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.779

Genes affected

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

LOC124903086 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-129074004-G-A is Benign according to our data. Variant chr12-129074004-G-A is described in ClinVar as [Benign]. Clinvar id is 3040259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.779 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3	c.3171C>T	p.Asp1057=	synonymous_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1	n.86+163G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7	c.3171C>T	p.Asp1057=	synonymous_variant	9/9	1	NM_133448.3	P1
TMEM132D	ENST00000389441.8	c.1785C>T	p.Asp595=	synonymous_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 69 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00675

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000644 AC: 162 AN: 251382 Hom.: 1 AF XY: 0.000508 AC XY: 69 AN XY: 135860

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00750

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000410 AC: 600 AN: 1461748 Hom.: 4 Cov.: 30 AF XY: 0.000402 AC XY: 292 AN XY: 727146

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74410

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00677

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.0000635 Hom.: 0

Bravo AF: 0.000370

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TMEM132D-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 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
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.22
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs74724941; hg19: chr12-129558549; COSMIC: COSV101242662;