rs1858359

Variant names:

• chr15-54357162-G-A
• rs1858359
• NM_001080534.3:c.4713+18673G>A

Variant summary

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

The NM_001080534.3(UNC13C):​c.4713+18673G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,658 control chromosomes in the GnomAD database, including 17,445 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 0.47 (17445 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 3 publications found

Genes affected

UNC13C (HGNC:23149): (unc-13 homolog C) Predicted to enable calmodulin binding activity and syntaxin-1 binding activity. Predicted to be involved in several processes, including glutamatergic synaptic transmission; regulated exocytosis; and synaptic vesicle maturation. Predicted to be located in presynaptic active zone. Predicted to be active in several cellular components, including axon terminus; parallel fiber to Purkinje cell synapse; and presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080534.3. 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
	UNC13C	NM_001080534.3	MANE Select	c.4713+18673G>A		intron	N/A	NP_001074003.1	Q8NB66
	UNC13C	NM_001329919.2		c.4707+18673G>A		intron	N/A	NP_001316848.1	A0A3B3ISZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13C	ENST00000260323.16	TSL:5 MANE Select	c.4713+18673G>A		intron	N/A	ENSP00000260323.11	Q8NB66
	UNC13C	ENST00000561210.1	TSL:1	n.1288+18673G>A		intron	N/A
	UNC13C	ENST00000647821.1		c.4707+18673G>A		intron	N/A	ENSP00000497525.1	A0A3B3ISZ1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71586 AN: 151538 Hom.: 17436 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.472 AC: 71640 AN: 151658 Hom.: 17445 Cov.: 32 AF XY: 0.476 AC XY: 35304 AN XY: 74114

African (AFR) AF: 0.499 AC: 20675 AN: 41402

American (AMR) AF: 0.394 AC: 6014 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4223 AN: 5160

South Asian (SAS) AF: 0.510 AC: 2451 AN: 4806

European-Finnish (FIN) AF: 0.521 AC: 5447 AN: 10462

Middle Eastern (MID) AF: 0.438 AC: 126 AN: 288

European-Non Finnish (NFE) AF: 0.435 AC: 29467 AN: 67804

Other (OTH) AF: 0.470 AC: 991 AN: 2108

Alfa AF: 0.439 Hom.: 14057

Bravo AF: 0.464

Asia WGS AF: 0.644 AC: 2201 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
DANN	Benign	0.66
PhyloP100		-0.55
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: rs1858359; hg19: chr15-54649360; COSMIC: COSV105821776;