rs17271305

Positions:

• chr15-62040781-A-G
• chr15-62040781-A-T

Variant summary

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

The NM_020821.3(VPS13C):​c.187+543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,036 control chromosomes in the GnomAD database, including 8,505 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 0.31 (8505 hom., cov: 32)
• Consequence: VPS13C NM_020821.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765

Genes affected

VPS13C (HGNC:23594): (vacuolar protein sorting 13 homolog C) Involved in mitochondrion organization and negative regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization. Located in cytosol and mitochondrial outer membrane. Implicated in Parkinson's disease 23. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13C	NM_020821.3	c.187+543T>C		intron_variant		ENST00000644861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13C	ENST00000644861.2	c.187+543T>C		intron_variant			NM_020821.3	P3
VPS13C	ENST00000249837.7	c.187+543T>C		intron_variant		1
VPS13C	ENST00000395898.3	c.187+543T>C		intron_variant		1
VPS13C	ENST00000645819.1	c.187+543T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47021 AN: 151918 Hom.: 8502 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.309 AC: 47037 AN: 152036 Hom.: 8505 Cov.: 32 AF XY: 0.314 AC XY: 23309 AN XY: 74326

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.319

Alfa AF: 0.368 Hom.: 18405

Bravo AF: 0.293

Asia WGS AF: 0.193 AC: 674 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.73

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: rs17271305; hg19: chr15-62332980;