chr15-62046598-G-T

Variant names:

• chr15-62046598-G-T
• rs1436958
• NM_020821.3:c.101-2343C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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]

VPS13C Gene-Disease associations (from GenCC):

• autosomal recessive early-onset Parkinson disease 23

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020821.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	NM_020821.3	MANE Select	c.101-2343C>A		intron	N/A	NP_065872.1
	VPS13C	NM_017684.5		c.101-2343C>A		intron	N/A	NP_060154.3
	VPS13C	NM_001018088.3		c.101-2343C>A		intron	N/A	NP_001018098.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	ENST00000644861.2	MANE Select	c.101-2343C>A		intron	N/A	ENSP00000493560.2
	VPS13C	ENST00000249837.7	TSL:1	c.101-2343C>A		intron	N/A	ENSP00000249837.3
	VPS13C	ENST00000395898.3	TSL:1	c.101-2343C>A		intron	N/A	ENSP00000379235.3

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

African (AFR) AF: 0.219 AC: 9071 AN: 41478

American (AMR) AF: 0.497 AC: 7595 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1817 AN: 5170

South Asian (SAS) AF: 0.371 AC: 1786 AN: 4816

European-Finnish (FIN) AF: 0.617 AC: 6507 AN: 10550

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 28037 AN: 67970

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.377 Hom.: 11166

Bravo AF: 0.362

Asia WGS AF: 0.346 AC: 1207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.021
DANN	Benign	0.61
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1436958; hg19: chr15-62338797;