15-62046598-G-T

Position:

• chr15-62046598-G-T

Variant summary

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

The NM_020821.3(VPS13C):​c.101-2343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,040 control chromosomes in the GnomAD database, including 11,815 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 0.38 (11815 hom., cov: 32)
• Consequence: VPS13C NM_020821.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13C	NM_020821.3	c.101-2343C>A		intron_variant		ENST00000644861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13C	ENST00000644861.2	c.101-2343C>A		intron_variant			NM_020821.3	P3
VPS13C	ENST00000249837.7	c.101-2343C>A		intron_variant		1
VPS13C	ENST00000395898.3	c.101-2343C>A		intron_variant		1
VPS13C	ENST00000645819.1	c.101-2343C>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57210 AN: 151922 Hom.: 11801 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.377 AC: 57245 AN: 152040 Hom.: 11815 Cov.: 32 AF XY: 0.387 AC XY: 28759 AN XY: 74310

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.382

Alfa AF: 0.403 Hom.: 6460

Bravo AF: 0.362

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.021
DANN	Benign	0.61

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: rs1436958; hg19: chr15-62338797;