12-129470814-T-C

Variant names:

• chr12-129470814-T-C
• rs7309727
• NM_133448.3:c.1115+60245A>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+60245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,070 control chromosomes in the GnomAD database, including 42,124 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 0.74 (42124 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 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.1115+60245A>G		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.1115+60245A>G		intron	N/A	ENSP00000408581.2

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113067 AN: 151952 Hom.: 42096 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.744 AC: 113137 AN: 152070 Hom.: 42124 Cov.: 32 AF XY: 0.744 AC XY: 55305 AN XY: 74344

African (AFR) AF: 0.738 AC: 30623 AN: 41480

American (AMR) AF: 0.718 AC: 10970 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2684 AN: 3472

East Asian (EAS) AF: 0.625 AC: 3219 AN: 5148

South Asian (SAS) AF: 0.691 AC: 3333 AN: 4822

European-Finnish (FIN) AF: 0.773 AC: 8157 AN: 10556

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51674 AN: 68006

Other (OTH) AF: 0.753 AC: 1590 AN: 2112

Alfa AF: 0.753 Hom.: 181605

Bravo AF: 0.743

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7309727; hg19: chr12-129955359;