15-54583363-A-T

Variant names:

• chr15-54583363-A-T
• rs746321
• NM_001080534.3:c.6106+15416A>T

Variant summary

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

The NM_001080534.3(UNC13C):​c.6106+15416A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,074 control chromosomes in the GnomAD database, including 31,188 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 0.63 (31188 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.6106+15416A>T		intron_variant	Intron 30 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.6106+15416A>T		intron_variant	Intron 30 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.6100+15416A>T		intron_variant	Intron 29 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96430 AN: 151958 Hom.: 31142 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.635 AC: 96534 AN: 152074 Hom.: 31188 Cov.: 32 AF XY: 0.630 AC XY: 46862 AN XY: 74336

African (AFR) AF: 0.717 AC: 29757 AN: 41502

American (AMR) AF: 0.682 AC: 10411 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2171 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1706 AN: 5174

South Asian (SAS) AF: 0.526 AC: 2535 AN: 4822

European-Finnish (FIN) AF: 0.580 AC: 6122 AN: 10558

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41684 AN: 67962

Other (OTH) AF: 0.645 AC: 1362 AN: 2110

Alfa AF: 0.619 Hom.: 3658

Bravo AF: 0.650

Asia WGS AF: 0.468 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		0.53
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: rs746321; hg19: chr15-54875561;