12-129152803-C-T

Variant names:

• chr12-129152803-C-T
• rs12824981
• NM_133448.3:c.1443+56717G>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.1443+56717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,148 control chromosomes in the GnomAD database, including 9,512 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 0.33 (9512 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.1443+56717G>A		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+56717G>A		intron_variant	Intron 5 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50071 AN: 152030 Hom.: 9507 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.329 AC: 50094 AN: 152148 Hom.: 9512 Cov.: 32 AF XY: 0.329 AC XY: 24487 AN XY: 74370

African (AFR) AF: 0.175 AC: 7248 AN: 41506

American (AMR) AF: 0.296 AC: 4521 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3468

East Asian (EAS) AF: 0.0988 AC: 511 AN: 5174

South Asian (SAS) AF: 0.198 AC: 953 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5410 AN: 10590

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.426 AC: 28959 AN: 67988

Other (OTH) AF: 0.313 AC: 662 AN: 2114

Alfa AF: 0.383 Hom.: 35734

Bravo AF: 0.308

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.34
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: rs12824981; hg19: chr12-129637348;