chr15-62040781-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020821.3(VPS13C):​c.187+543T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13C	NM_020821.3	c.187+543T>A		intron_variant	Intron 3 of 84	ENST00000644861.2	NP_065872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13C	ENST00000644861.2	c.187+543T>A		intron_variant	Intron 3 of 84		NM_020821.3	ENSP00000493560.2
VPS13C	ENST00000249837.7	c.187+543T>A		intron_variant	Intron 3 of 82	1		ENSP00000249837.3
VPS13C	ENST00000395898.3	c.187+543T>A		intron_variant	Intron 3 of 79	1		ENSP00000379235.3
VPS13C	ENST00000645819.1	c.187+543T>A		intron_variant	Intron 3 of 81			ENSP00000496179.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 38260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		0.77

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;