15-61854399-C-T

Variant names:

• chr15-61854399-C-T
• rs17238096
• NM_020821.3:c.*58G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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)

ENSG00000259564 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020821.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	NM_020821.3	MANE Select	c.*58G>A		3_prime_UTR	Exon 85 of 85	NP_065872.1	Q709C8-1
	VPS13C	NM_017684.5		c.*58G>A		3_prime_UTR	Exon 83 of 83	NP_060154.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	ENST00000644861.2	MANE Select	c.*58G>A		3_prime_UTR	Exon 85 of 85	ENSP00000493560.2	Q709C8-1
	VPS13C	ENST00000249837.7	TSL:1	c.*58G>A		3_prime_UTR	Exon 83 of 83	ENSP00000249837.3	Q709C8-3
	VPS13C	ENST00000560637.5	TSL:1	n.1689G>A		non_coding_transcript_exon	Exon 4 of 4

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

African (AFR) AF: 0.0297 AC: 909 AN: 30574

American (AMR) AF: 0.0472 AC: 2101 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 1257 AN: 25250

East Asian (EAS) AF: 0.0354 AC: 1380 AN: 39016

South Asian (SAS) AF: 0.0633 AC: 5275 AN: 83344

European-Finnish (FIN) AF: 0.0384 AC: 2047 AN: 53356

Middle Eastern (MID) AF: 0.0831 AC: 456 AN: 5486

European-Non Finnish (NFE) AF: 0.0786 AC: 77087 AN: 980292

Other (OTH) AF: 0.0702 AC: 3904 AN: 55626

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

African (AFR) AF: 0.0279 AC: 1159 AN: 41526

American (AMR) AF: 0.0650 AC: 993 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.0369 AC: 191 AN: 5176

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4826

European-Finnish (FIN) AF: 0.0341 AC: 362 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5419 AN: 67988

Other (OTH) AF: 0.0712 AC: 150 AN: 2108

Alfa AF: 0.0730 Hom.: 756

Bravo AF: 0.0593

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.70
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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