rs2253306

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.890 AC: 36983 AN: 41532

American (AMR) AF: 0.975 AC: 14917 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3443 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4040 AN: 5170

South Asian (SAS) AF: 0.827 AC: 3988 AN: 4822

European-Finnish (FIN) AF: 0.943 AC: 9998 AN: 10598

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65694 AN: 68042

Other (OTH) AF: 0.947 AC: 1995 AN: 2106

Alfa AF: 0.954 Hom.: 14119

Bravo AF: 0.936

Asia WGS AF: 0.814 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.24
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs2253306; hg19: chr15-54212323;