rs4759966

Variant names:

• chr12-129554313-C-A
• rs4759966
• NM_133448.3:c.969-23108G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-129554313-C-A
• chr12-129554313-C-G
• chr12-129554313-C-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.969-23108G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,150 control chromosomes in the GnomAD database, including 56,993 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 0.86 (56993 hom., cov: 32)
• Consequence: TMEM132D NM_133448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	NM_133448.3	MANE Select	c.969-23108G>T		intron	N/A	NP_597705.2	Q14C87-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132D	ENST00000422113.7	TSL:1 MANE Select	c.969-23108G>T		intron	N/A	ENSP00000408581.2	Q14C87-1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131487 AN: 152032 Hom.: 56942 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.848

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

GnomAD4 genome AF: 0.865 AC: 131592 AN: 152150 Hom.: 56993 Cov.: 32 AF XY: 0.870 AC XY: 64684 AN XY: 74370

African (AFR) AF: 0.859 AC: 35645 AN: 41500

American (AMR) AF: 0.881 AC: 13478 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2733 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5095 AN: 5158

South Asian (SAS) AF: 0.885 AC: 4265 AN: 4818

European-Finnish (FIN) AF: 0.901 AC: 9537 AN: 10588

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.853 AC: 58013 AN: 68008

Other (OTH) AF: 0.849 AC: 1793 AN: 2112

Alfa AF: 0.863 Hom.: 5209

Bravo AF: 0.868

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.68
DANN	Benign	0.34
PhyloP100		-0.30
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: rs4759966; hg19: chr12-130038858;