15-54483002-C-T

Variant names:

• chr15-54483002-C-T
• rs885203
• NM_001080534.3:c.4934-11606C>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.4934-11606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,936 control chromosomes in the GnomAD database, including 13,257 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 0.41 (13257 hom., cov: 32)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.4934-11606C>T		intron_variant	Intron 19 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.4934-11606C>T		intron_variant	Intron 19 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000647821.1	c.4928-11606C>T		intron_variant	Intron 18 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62746 AN: 151818 Hom.: 13250 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.413 AC: 62794 AN: 151936 Hom.: 13257 Cov.: 32 AF XY: 0.417 AC XY: 30978 AN XY: 74264

African (AFR) AF: 0.440 AC: 18204 AN: 41418

American (AMR) AF: 0.363 AC: 5535 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.625 AC: 3232 AN: 5168

South Asian (SAS) AF: 0.466 AC: 2241 AN: 4806

European-Finnish (FIN) AF: 0.409 AC: 4315 AN: 10538

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.390 AC: 26483 AN: 67966

Other (OTH) AF: 0.384 AC: 812 AN: 2112

Alfa AF: 0.306 Hom.: 1147

Bravo AF: 0.407

Asia WGS AF: 0.515 AC: 1785 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.7
DANN	Benign	0.37
PhyloP100		0.14
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: rs885203; hg19: chr15-54775200;