15-54315929-A-G

Variant names:

• chr15-54315929-A-G
• rs4457945
• NM_001080534.3:c.4269-6010A>G

Variant summary

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

The NM_001080534.3(UNC13C):​c.4269-6010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,508 control chromosomes in the GnomAD database, including 6,985 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 0.29 (6985 hom., cov: 30)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 4 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 (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	NM_001080534.3	c.4269-6010A>G		intron_variant	Intron 13 of 32	ENST00000260323.16	NP_001074003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13C	ENST00000260323.16	c.4269-6010A>G		intron_variant	Intron 13 of 32	5	NM_001080534.3	ENSP00000260323.11
UNC13C	ENST00000561210.1	n.844-6010A>G		intron_variant	Intron 5 of 11	1
UNC13C	ENST00000647821.1	c.4263-6010A>G		intron_variant	Intron 12 of 31			ENSP00000497525.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44444 AN: 151388 Hom.: 6958 Cov.: 30

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.294 AC: 44522 AN: 151508 Hom.: 6985 Cov.: 30 AF XY: 0.294 AC XY: 21760 AN XY: 73996

African (AFR) AF: 0.197 AC: 8161 AN: 41382

American (AMR) AF: 0.378 AC: 5741 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1101 AN: 3460

East Asian (EAS) AF: 0.303 AC: 1537 AN: 5076

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4810

European-Finnish (FIN) AF: 0.359 AC: 3788 AN: 10552

Middle Eastern (MID) AF: 0.319 AC: 92 AN: 288

European-Non Finnish (NFE) AF: 0.327 AC: 22137 AN: 67738

Other (OTH) AF: 0.323 AC: 678 AN: 2102

Alfa AF: 0.313 Hom.: 12824

Bravo AF: 0.293

Asia WGS AF: 0.278 AC: 968 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.85
DANN	Benign	0.51
PhyloP100		-0.40
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: rs4457945; hg19: chr15-54608127;