12-129226901-G-A

Position:

• chr12-129226901-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133448.3(TMEM132D):​c.1300-17238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,098 control chromosomes in the GnomAD database, including 2,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2993 hom., cov: 31)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3	c.1300-17238C>T		intron_variant		ENST00000422113.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7	c.1300-17238C>T		intron_variant		1	NM_133448.3	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29226 AN: 151978 Hom.: 2989 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29249 AN: 152098 Hom.: 2993 Cov.: 31 AF XY: 0.187 AC XY: 13931 AN XY: 74326

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.196

Alfa AF: 0.192 Hom.: 606

Bravo AF: 0.192

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.71

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: rs12371373; hg19: chr12-129711446;