rs2253306

Variant names:

• chr15-53920126-C-T
• rs2253306
• XM_017022220.2:c.-257+1832C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017022220.2(UNC13C):​c.-257+1832C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,240 control chromosomes in the GnomAD database, including 66,650 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 0.93 (66650 hom., cov: 33)
• Consequence: UNC13C XM_017022220.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13C	XM_017022220.2	c.-257+1832C>T		intron_variant	Intron 5 of 36		XP_016877709.1
UNC13C	XM_017022221.2	c.-257+1832C>T		intron_variant	Intron 4 of 35		XP_016877710.1
UNC13C	XM_017022222.2	c.-257+41828C>T		intron_variant	Intron 3 of 34		XP_016877711.1
UNC13C	XM_047432538.1	c.-257+1832C>T		intron_variant	Intron 6 of 37		XP_047288494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142157 AN: 152122 Hom.: 66633 Cov.: 33

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.934 AC: 142223 AN: 152240 Hom.: 66650 Cov.: 33 AF XY: 0.931 AC XY: 69276 AN XY: 74450

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.947

Alfa AF: 0.955 Hom.: 13797

Bravo AF: 0.936

Asia WGS AF: 0.814 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2253306; hg19: chr15-54212323;