chr12-129226901-G-A

Variant names:

• chr12-129226901-G-A
• rs12371373
• NM_133448.3:c.1300-17238C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

Genes affected

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

TMEM132D Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.1300-17238C>T		intron_variant	Intron 4 of 8	ENST00000422113.7	NP_597705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7	c.1300-17238C>T		intron_variant	Intron 4 of 8	1	NM_133448.3	ENSP00000408581.2

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

African (AFR) AF: 0.180 AC: 7486 AN: 41478

American (AMR) AF: 0.140 AC: 2143 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5164

South Asian (SAS) AF: 0.106 AC: 510 AN: 4816

European-Finnish (FIN) AF: 0.197 AC: 2088 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14654 AN: 67992

Other (OTH) AF: 0.196 AC: 413 AN: 2102

Alfa AF: 0.191 Hom.: 1067

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12371373; hg19: chr12-129711446;