12-129073992-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_133448.3(TMEM132D):c.3183C>T(p.Thr1061=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,952 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (10 hom., cov: 32)
  • Exomes 𝑓: 0.013 (170 hom.)
• Consequence: TMEM132D NM_133448.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.584

Genes affected

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

LOC124903086 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-129073992-G-A is Benign according to our data. Variant chr12-129073992-G-A is described in ClinVar as [Benign]. Clinvar id is 773268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.584 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0127 (18566/1461732) while in subpopulation NFE AF= 0.0153 (17000/1111906). AF 95% confidence interval is 0.0151. There are 170 homozygotes in gnomad4_exome. There are 8992 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3	c.3183C>T	p.Thr1061=	synonymous_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1	n.86+151G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7	c.3183C>T	p.Thr1061=	synonymous_variant	9/9	1	NM_133448.3	P1
TMEM132D	ENST00000389441.8	c.1797C>T	p.Thr599=	synonymous_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.00844 AC: 1283 AN: 152102 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00693

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00809 AC: 2034 AN: 251380 Hom.: 12 AF XY: 0.00829 AC XY: 1127 AN XY: 135868

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00631

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00141

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.0127 AC: 18566 AN: 1461732 Hom.: 170 Cov.: 30 AF XY: 0.0124 AC XY: 8992 AN XY: 727144

Gnomad4 AFR exome AF: 0.00275

Gnomad4 AMR exome AF: 0.00633

Gnomad4 ASJ exome AF: 0.00635

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.00359

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.00843 AC: 1283 AN: 152220 Hom.: 10 Cov.: 32 AF XY: 0.00747 AC XY: 556 AN XY: 74416

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00693

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.0110 Hom.: 7

Bravo AF: 0.00891

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0155

EpiControl AF: 0.0163

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.28
Dann	Benign	0.52

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: rs74344050; hg19: chr12-129558537;