15-61855008-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020821.3(VPS13C):c.11077-54A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,469,650 control chromosomes in the GnomAD database, including 106,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9794 hom., cov: 32)
  • Exomes 𝑓: 0.38 (96473 hom.)
• Consequence: VPS13C NM_020821.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-61855008-T-A is Benign according to our data. Variant chr15-61855008-T-A is described in ClinVar as [Benign]. Clinvar id is 1283776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13C	NM_020821.3	c.11077-54A>T		intron_variant		ENST00000644861.2
LOC124903501	XR_007064668.1	n.159+5536T>A		intron_variant, non_coding_transcript_variant
VPS13C	NM_017684.5	c.10948-54A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13C	ENST00000644861.2	c.11077-54A>T		intron_variant			NM_020821.3	P3
	ENST00000642740.1	n.172+5536T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53867 AN: 151802 Hom.: 9785 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.382 AC: 503194 AN: 1317730 Hom.: 96473 AF XY: 0.382 AC XY: 249651 AN XY: 653820

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.355 AC: 53897 AN: 151920 Hom.: 9794 Cov.: 32 AF XY: 0.355 AC XY: 26323 AN XY: 74252

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.371

Alfa AF: 0.273 Hom.: 775

Bravo AF: 0.354

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.5
Dann	Benign	0.43

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: rs2241492; hg19: chr15-62147207; COSMIC: COSV51424088; COSMIC: COSV51424088;