15-53964061-T-C

Variant names:

• chr15-53964061-T-C
• rs8027521
• XM_017022220.2:c.-257+45767T>C

Variant summary

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

The ENST00000558866.5(ENSG00000259669):​n.397+3941A>G 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: ENSG00000259669 ENST00000558866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• 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]

ENSG00000259669 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000259669	ENST00000557976.6	TSL:5	n.1520+3941A>G		intron	N/A
	ENSG00000259669	ENST00000558866.5	TSL:3	n.397+3941A>G		intron	N/A
	ENSG00000259669	ENST00000558920.1	TSL:3	n.267-8230A>G		intron	N/A

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

African (AFR) AF: 0.506 AC: 20983 AN: 41450

American (AMR) AF: 0.438 AC: 6689 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1714 AN: 3464

East Asian (EAS) AF: 0.535 AC: 2764 AN: 5164

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4820

European-Finnish (FIN) AF: 0.632 AC: 6655 AN: 10536

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35783 AN: 67968

Other (OTH) AF: 0.522 AC: 1101 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.79
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs8027521; hg19: chr15-54256258;