rs12608932

Variant names:

• chr19-17641880-A-C
• rs12608932
• NM_001080421.3:c.2473-324T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-17641880-A-C
• chr19-17641880-A-T

Variant summary

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

The NM_001080421.3(UNC13A):​c.2473-324T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,542 control chromosomes in the GnomAD database, including 10,546 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 0.36 (10546 hom., cov: 30)
• Consequence: UNC13A NM_001080421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 92 publications found

Genes affected

UNC13A (HGNC:23150): (unc-13 homolog A) This gene encodes a member of the UNC13 family. UNC13 proteins bind to phorbol esters and diacylglycerol and play important roles in neurotransmitter release at synapses. Single nucleotide polymorphisms in this gene may be associated with sporadic amyotrophic lateral sclerosis. [provided by RefSeq, Feb 2012]

UNC13A Gene-Disease associations (from GenCC):

• congenital nervous system disorder

  Inheritance: Unknown Classification: LIMITED Submitted by: Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080421.3. 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
	UNC13A	NM_001080421.3	MANE Select	c.2473-324T>G		intron	N/A	NP_001073890.2	Q9UPW8
	UNC13A	NM_001387021.1		c.2467-324T>G		intron	N/A	NP_001373950.1
	UNC13A	NM_001387022.1		c.2467-324T>G		intron	N/A	NP_001373951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13A	ENST00000519716.7	TSL:5 MANE Select	c.2473-324T>G		intron	N/A	ENSP00000429562.2	Q9UPW8
	UNC13A	ENST00000551649.5	TSL:5	c.2473-324T>G		intron	N/A	ENSP00000447236.1	F8W059
	UNC13A	ENST00000552293.5	TSL:5	c.2473-324T>G		intron	N/A	ENSP00000447572.1	F8W0P6

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55282 AN: 151422 Hom.: 10551 Cov.: 30

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.365 AC: 55290 AN: 151542 Hom.: 10546 Cov.: 30 AF XY: 0.374 AC XY: 27688 AN XY: 74054

African (AFR) AF: 0.342 AC: 14118 AN: 41304

American (AMR) AF: 0.361 AC: 5499 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3555 AN: 5154

South Asian (SAS) AF: 0.448 AC: 2149 AN: 4798

European-Finnish (FIN) AF: 0.467 AC: 4893 AN: 10480

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23106 AN: 67806

Other (OTH) AF: 0.326 AC: 686 AN: 2104

Alfa AF: 0.347 Hom.: 33420

Bravo AF: 0.349

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.55
PhyloP100		-2.1
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: rs12608932; hg19: chr19-17752689;