15-61854770-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.11160+101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,169,994 control chromosomes in the GnomAD database, including 174,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22378 hom., cov: 31)
  • Exomes 𝑓: 0.54 (152148 hom.)
• Consequence: VPS13C NM_020821.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128

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=-0.96).
• BP6: Variant 15-61854770-T-A is Benign according to our data. Variant chr15-61854770-T-A is described in ClinVar as [Benign]. Clinvar id is 1241074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13C	NM_020821.3	c.11160+101A>T		intron_variant		ENST00000644861.2
LOC124903501	XR_007064668.1	n.159+5298T>A		intron_variant, non_coding_transcript_variant
VPS13C	NM_017684.5	c.11031+101A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13C	ENST00000644861.2	c.11160+101A>T		intron_variant			NM_020821.3	P3
	ENST00000642740.1	n.172+5298T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81802 AN: 151806 Hom.: 22352 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.544 AC: 553575 AN: 1018070 Hom.: 152148 AF XY: 0.541 AC XY: 277078 AN XY: 512586

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.674

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.539 AC: 81874 AN: 151924 Hom.: 22378 Cov.: 31 AF XY: 0.545 AC XY: 40438 AN XY: 74252

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.532

Alfa AF: 0.551 Hom.: 2800

Bravo AF: 0.532

Asia WGS AF: 0.482 AC: 1676 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.8
Dann	Benign	0.51

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: rs2241491; hg19: chr15-62146969; COSMIC: COSV51160737; COSMIC: COSV51160737;