rs11060369

Variant names:

• chr12-129475652-A-C
• rs11060369
• NM_133448.3:c.1115+55407T>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.1115+55407T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,078 control chromosomes in the GnomAD database, including 13,024 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 0.41 (13024 hom., cov: 33)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 17 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132D	NM_133448.3	c.1115+55407T>G		intron_variant	Intron 3 of 8	ENST00000422113.7	NP_597705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132D	ENST00000422113.7	c.1115+55407T>G		intron_variant	Intron 3 of 8	1	NM_133448.3	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62049 AN: 151960 Hom.: 13002 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.408 AC: 62107 AN: 152078 Hom.: 13024 Cov.: 33 AF XY: 0.412 AC XY: 30607 AN XY: 74358

African (AFR) AF: 0.512 AC: 21241 AN: 41462

American (AMR) AF: 0.388 AC: 5929 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2118 AN: 5176

South Asian (SAS) AF: 0.416 AC: 2006 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4054 AN: 10586

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24220 AN: 67974

Other (OTH) AF: 0.370 AC: 778 AN: 2104

Alfa AF: 0.364 Hom.: 13855

Bravo AF: 0.410

Asia WGS AF: 0.404 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.72
PhyloP100		1.9
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: rs11060369; hg19: chr12-129960197;