15-61854399-C-T

Position:

• chr15-61854399-C-T

Variant summary

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

The NM_020821.3(VPS13C):​c.*58G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 1,469,670 control chromosomes in the GnomAD database, including 3,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (314 hom., cov: 32)
  • Exomes 𝑓: 0.072 (3680 hom.)
• Consequence: VPS13C NM_020821.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.467

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-61854399-C-T is Benign according to our data. Variant chr15-61854399-C-T is described in ClinVar as [Benign]. Clinvar id is 1238891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13C	NM_020821.3	c.*58G>A		3_prime_UTR_variant	85/85	ENST00000644861.2	NP_065872.1
VPS13C	NM_017684.5	c.*58G>A		3_prime_UTR_variant	83/83		NP_060154.3
LOC124903501	XR_007064668.1	n.159+4927C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13C	ENST00000644861	c.*58G>A		3_prime_UTR_variant	85/85		NM_020821.3	ENSP00000493560.2

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8821 AN: 152076 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0341

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0719

GnomAD4 exome AF: 0.0717 AC: 94416 AN: 1317476 Hom.: 3680 Cov.: 20 AF XY: 0.0719 AC XY: 47647 AN XY: 662858

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.0472

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.0633

Gnomad4 FIN exome AF: 0.0384

Gnomad4 NFE exome AF: 0.0786

Gnomad4 OTH exome AF: 0.0702

GnomAD4 genome AF: 0.0579 AC: 8818 AN: 152194 Hom.: 314 Cov.: 32 AF XY: 0.0559 AC XY: 4159 AN XY: 74426

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.0341

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.0712

Alfa AF: 0.0745 Hom.: 634

Bravo AF: 0.0593

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.70

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: rs17238096; hg19: chr15-62146598; COSMIC: COSV51188111; COSMIC: COSV51188111;