15-62040781-A-G

Variant names:

• chr15-62040781-A-G
• rs17271305
• NM_020821.3:c.187+543T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	NM_020821.3	MANE Select	c.187+543T>C		intron	N/A	NP_065872.1	Q709C8-1
	VPS13C	NM_017684.5		c.187+543T>C		intron	N/A	NP_060154.3
	VPS13C	NM_001018088.3		c.187+543T>C		intron	N/A	NP_001018098.1	Q709C8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	ENST00000644861.2	MANE Select	c.187+543T>C		intron	N/A	ENSP00000493560.2	Q709C8-1
	VPS13C	ENST00000249837.7	TSL:1	c.187+543T>C		intron	N/A	ENSP00000249837.3	Q709C8-3
	VPS13C	ENST00000395898.3	TSL:1	c.187+543T>C		intron	N/A	ENSP00000379235.3	Q709C8-4

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

African (AFR) AF: 0.120 AC: 4986 AN: 41524

American (AMR) AF: 0.371 AC: 5674 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1230 AN: 3468

East Asian (EAS) AF: 0.149 AC: 772 AN: 5182

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4816

European-Finnish (FIN) AF: 0.510 AC: 5361 AN: 10502

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26709 AN: 67950

Other (OTH) AF: 0.319 AC: 673 AN: 2108

Alfa AF: 0.358 Hom.: 38260

Bravo AF: 0.293

Asia WGS AF: 0.193 AC: 674 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.77
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: rs17271305; hg19: chr15-62332980;