12-129538158-C-G

Variant names:

• chr12-129538158-C-G
• rs2170820
• NM_133448.3:c.969-6953G>C

Variant summary

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

The NM_133448.3(TMEM132D):​c.969-6953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,146 control chromosomes in the GnomAD database, including 34,179 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 0.67 (34179 hom., cov: 33)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.969-6953G>C		intron_variant	Intron 2 of 8	ENST00000422113.7	NP_597705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7	c.969-6953G>C		intron_variant	Intron 2 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101091 AN: 152028 Hom.: 34144 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.665 AC: 101183 AN: 152146 Hom.: 34179 Cov.: 33 AF XY: 0.667 AC XY: 49637 AN XY: 74370

African (AFR) AF: 0.760 AC: 31540 AN: 41516

American (AMR) AF: 0.668 AC: 10212 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1718 AN: 3466

East Asian (EAS) AF: 0.926 AC: 4804 AN: 5190

South Asian (SAS) AF: 0.668 AC: 3218 AN: 4818

European-Finnish (FIN) AF: 0.610 AC: 6440 AN: 10558

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41121 AN: 67998

Other (OTH) AF: 0.633 AC: 1338 AN: 2114

Alfa AF: 0.629 Hom.: 3562

Bravo AF: 0.674

Asia WGS AF: 0.772 AC: 2684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.28
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: rs2170820; hg19: chr12-130022703;