chr12-129162056-T-C

Variant names:

• chr12-129162056-T-C
• rs12580533
• NM_133448.3:c.1443+47464A>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.1443+47464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,090 control chromosomes in the GnomAD database, including 1,029 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 0.077 (1029 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.1443+47464A>G		intron_variant	Intron 5 of 8	ENST00000422113.7	NP_597705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7	c.1443+47464A>G		intron_variant	Intron 5 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11706 AN: 151972 Hom.: 1024 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.00368

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0772 AC: 11740 AN: 152090 Hom.: 1029 Cov.: 32 AF XY: 0.0771 AC XY: 5733 AN XY: 74370

African (AFR) AF: 0.209 AC: 8679 AN: 41454

American (AMR) AF: 0.0639 AC: 976 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.144 AC: 742 AN: 5170

South Asian (SAS) AF: 0.0492 AC: 236 AN: 4796

European-Finnish (FIN) AF: 0.00368 AC: 39 AN: 10594

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 914 AN: 68002

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0458 Hom.: 797

Bravo AF: 0.0858

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.70
PhyloP100		-1.1
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: rs12580533; hg19: chr12-129646601;