12-129226246-G-A

Variant names:

• chr12-129226246-G-A
• rs1482294
• NM_133448.3:c.1300-16583C>T

Variant summary

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

The NM_133448.3(TMEM132D):​c.1300-16583C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,842 control chromosomes in the GnomAD database, including 17,133 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 0.47 (17133 hom., cov: 33)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	NM_133448.3	MANE Select	c.1300-16583C>T		intron	N/A	NP_597705.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	ENST00000422113.7	TSL:1 MANE Select	c.1300-16583C>T		intron	N/A	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70609 AN: 151722 Hom.: 17110 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.465 AC: 70672 AN: 151842 Hom.: 17133 Cov.: 33 AF XY: 0.475 AC XY: 35299 AN XY: 74250

African (AFR) AF: 0.444 AC: 18321 AN: 41236

American (AMR) AF: 0.551 AC: 8429 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3468

East Asian (EAS) AF: 0.850 AC: 4398 AN: 5174

South Asian (SAS) AF: 0.651 AC: 3137 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4874 AN: 10590

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28485 AN: 67960

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.446 Hom.: 12016

Bravo AF: 0.470

Asia WGS AF: 0.722 AC: 2509 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.81
PhyloP100		-0.66
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: rs1482294; hg19: chr12-129710791;