chr15-54357162-G-A

Position:

• chr15-54357162-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13C	NM_001080534.3	c.4713+18673G>A		intron_variant		ENST00000260323.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13C	ENST00000260323.16	c.4713+18673G>A		intron_variant		5	NM_001080534.3	A1
UNC13C	ENST00000561210.1	n.1288+18673G>A		intron_variant, non_coding_transcript_variant		1
UNC13C	ENST00000647821.1	c.4707+18673G>A		intron_variant				P4

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

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.470

Alfa AF: 0.438 Hom.: 11955

Bravo AF: 0.464

Asia WGS AF: 0.644 AC: 2201 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.78
DANN	Benign	0.66

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: rs1858359; hg19: chr15-54649360; COSMIC: COSV105821776;