chr15-62060644-C-T

Variant names:

• chr15-62060644-C-T
• rs11630347
• ENST00000560813.2:n.142C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000560813.2(VPS13C-DT):​n.142C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 228,424 control chromosomes in the GnomAD database, including 35,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23262 hom., cov: 33)
  • Exomes 𝑓: 0.55 (11740 hom.)
• Consequence: VPS13C-DT ENST00000560813.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0490

Genes affected

VPS13C-DT (HGNC:55425): (VPS13C divergent transcript)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-62060644-C-T is Benign according to our data. Variant chr15-62060644-C-T is described in ClinVar as [Benign]. Clinvar id is 1264379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13C	NM_020821.3	c.-270G>A		upstream_gene_variant		ENST00000644861.2	NP_065872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13C	ENST00000644861.2	c.-270G>A		upstream_gene_variant			NM_020821.3	ENSP00000493560.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83433 AN: 151938 Hom.: 23233 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.548 AC: 41871 AN: 76368 Hom.: 11740 Cov.: 0 AF XY: 0.545 AC XY: 21405 AN XY: 39310

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.678

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.721

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.549 AC: 83514 AN: 152056 Hom.: 23262 Cov.: 33 AF XY: 0.554 AC XY: 41188 AN XY: 74332

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.542

Alfa AF: 0.574 Hom.: 5570

Bravo AF: 0.544

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11630347; hg19: chr15-62352843;