rs265619

Variant names:

• chr12-129627134-C-G
• rs265619
• NM_133448.3:c.968+72676G>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.968+72676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,940 control chromosomes in the GnomAD database, including 10,644 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 0.37 (10644 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.968+72676G>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.968+72676G>C		intron_variant	Intron 2 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56375 AN: 151822 Hom.: 10627 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.371 AC: 56427 AN: 151940 Hom.: 10644 Cov.: 32 AF XY: 0.377 AC XY: 28015 AN XY: 74252

African (AFR) AF: 0.395 AC: 16353 AN: 41424

American (AMR) AF: 0.430 AC: 6570 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1768 AN: 5148

South Asian (SAS) AF: 0.420 AC: 2023 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4365 AN: 10524

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23146 AN: 67962

Other (OTH) AF: 0.332 AC: 701 AN: 2112

Alfa AF: 0.366 Hom.: 1388

Bravo AF: 0.375

Asia WGS AF: 0.346 AC: 1206 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	0.92
DANN	Benign	0.25
PhyloP100		-0.27
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: rs265619; hg19: chr12-130111679;