chr15-53964061-T-C

Position:

• chr15-53964061-T-C

Variant summary

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

The XM_017022220.2(UNC13C):​c.-257+45767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,980 control chromosomes in the GnomAD database, including 20,560 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 0.52 (20560 hom., cov: 32)
• Consequence: UNC13C XM_017022220.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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]

ENSG00000259669 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13C	XM_017022220.2	c.-257+45767T>C		intron_variant			XP_016877709.1
UNC13C	XM_017022221.2	c.-257+45767T>C		intron_variant			XP_016877710.1
UNC13C	XM_017022222.2	c.-256-48587T>C		intron_variant			XP_016877711.1
UNC13C	XM_047432538.1	c.-257+45767T>C		intron_variant			XP_047288494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000259669	ENST00000557976.6	n.1520+3941A>G		intron_variant		5
ENSG00000259669	ENST00000558866.5	n.397+3941A>G		intron_variant		3
ENSG00000259669	ENST00000558920.1	n.267-8230A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78700 AN: 151862 Hom.: 20555 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.518 AC: 78731 AN: 151980 Hom.: 20560 Cov.: 32 AF XY: 0.522 AC XY: 38778 AN XY: 74260

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.522

Alfa AF: 0.521 Hom.: 2599

Bravo AF: 0.501

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8027521; hg19: chr15-54256258;