12-129561207-T-C

Variant names:

• chr12-129561207-T-C
• rs155705
• NM_133448.3:c.969-30002A>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.969-30002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,184 control chromosomes in the GnomAD database, including 57,486 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 0.87 (57486 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 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.969-30002A>G		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.969-30002A>G		intron	N/A	ENSP00000408581.2	Q14C87-1

Frequencies

GnomAD3 genomes AF: 0.868 AC: 132002 AN: 152066 Hom.: 57419 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.868 AC: 132129 AN: 152184 Hom.: 57486 Cov.: 32 AF XY: 0.872 AC XY: 64844 AN XY: 74398

African (AFR) AF: 0.903 AC: 37479 AN: 41526

American (AMR) AF: 0.879 AC: 13438 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2639 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5111 AN: 5176

South Asian (SAS) AF: 0.859 AC: 4140 AN: 4818

European-Finnish (FIN) AF: 0.880 AC: 9320 AN: 10594

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57194 AN: 67996

Other (OTH) AF: 0.851 AC: 1793 AN: 2108

Alfa AF: 0.848 Hom.: 30982

Bravo AF: 0.871

Asia WGS AF: 0.928 AC: 3226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-2.0
Mutation Taster		=99/1	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: rs155705; hg19: chr12-130045752;