rs7134835

Variant names:

• chr12-129426125-T-C
• rs7134835
• NM_133448.3:c.1116-88308A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133448.3(TMEM132D):​c.1116-88308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,018 control chromosomes in the GnomAD database, including 7,748 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 0.30 (7748 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.1116-88308A>G		intron_variant	Intron 3 of 8	ENST00000422113.7	NP_597705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7	c.1116-88308A>G		intron_variant	Intron 3 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45147 AN: 151900 Hom.: 7736 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.297 AC: 45185 AN: 152018 Hom.: 7748 Cov.: 32 AF XY: 0.301 AC XY: 22387 AN XY: 74314

African (AFR) AF: 0.123 AC: 5094 AN: 41490

American (AMR) AF: 0.410 AC: 6251 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2469 AN: 5142

South Asian (SAS) AF: 0.235 AC: 1129 AN: 4812

European-Finnish (FIN) AF: 0.394 AC: 4166 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24257 AN: 67960

Other (OTH) AF: 0.310 AC: 654 AN: 2108

Alfa AF: 0.325 Hom.: 1802

Bravo AF: 0.293

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.37
PhyloP100		-1.9
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: rs7134835; hg19: chr12-129910670;