rs12608932

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13A	NM_001080421.3	c.2473-324T>G		intron_variant		ENST00000519716.7	NP_001073890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13A	ENST00000519716.7	c.2473-324T>G		intron_variant		5	NM_001080421.3	ENSP00000429562	A2
UNC13A	ENST00000550896.1	c.2467-324T>G		intron_variant		5		ENSP00000446831	A2
UNC13A	ENST00000551649.5	c.2473-324T>G		intron_variant		5		ENSP00000447236	P3
UNC13A	ENST00000552293.5	c.2473-324T>G		intron_variant		5		ENSP00000447572	A2

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

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.326

Alfa AF: 0.337 Hom.: 11965

Bravo AF: 0.349

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs12608932; hg19: chr19-17752689;