12-129592070-C-T

Variant names:

• chr12-129592070-C-T
• rs265634
• NM_133448.3:c.969-60865G>A

Variant summary

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

The NM_133448.3(TMEM132D):​c.969-60865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,950 control chromosomes in the GnomAD database, including 34,826 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 (34826 hom., cov: 33)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	NM_133448.3	MANE Select	c.969-60865G>A		intron	N/A	NP_597705.2	Q14C87-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	ENST00000422113.7	TSL:1 MANE Select	c.969-60865G>A		intron	N/A	ENSP00000408581.2	Q14C87-1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102472 AN: 151834 Hom.: 34800 Cov.: 33

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.675 AC: 102538 AN: 151950 Hom.: 34826 Cov.: 33 AF XY: 0.678 AC XY: 50357 AN XY: 74260

African (AFR) AF: 0.713 AC: 29499 AN: 41364

American (AMR) AF: 0.749 AC: 11460 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3472

East Asian (EAS) AF: 0.839 AC: 4336 AN: 5170

South Asian (SAS) AF: 0.689 AC: 3326 AN: 4824

European-Finnish (FIN) AF: 0.652 AC: 6874 AN: 10550

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42684 AN: 67968

Other (OTH) AF: 0.685 AC: 1444 AN: 2108

Alfa AF: 0.594 Hom.: 2659

Bravo AF: 0.686

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.2
DANN	Benign	0.46
PhyloP100		-0.085
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: rs265634; hg19: chr12-130076615;