15-61854971-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020821.3(VPS13C):c.11077-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,576,614 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (30 hom.)
• Consequence: VPS13C NM_020821.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.978

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=-0.56).
• BP6: Variant 15-61854971-A-G is Benign according to our data. Variant chr15-61854971-A-G is described in ClinVar as [Benign]. Clinvar id is 1535945.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1639/152318) while in subpopulation AFR AF= 0.0379 (1573/41558). AF 95% confidence interval is 0.0363. There are 32 homozygotes in gnomad4. There are 755 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13C	NM_020821.3	c.11077-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000644861.2
LOC124903501	XR_007064668.1	n.159+5499A>G		intron_variant, non_coding_transcript_variant
VPS13C	NM_017684.5	c.10948-17T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13C	ENST00000644861.2	c.11077-17T>C		splice_polypyrimidine_tract_variant, intron_variant			NM_020821.3	P3
	ENST00000642740.1	n.172+5499A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1619 AN: 152200 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00289 AC: 614 AN: 212160 Hom.: 12 AF XY: 0.00207 AC XY: 239 AN XY: 115184

Gnomad AFR exome AF: 0.0371

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000129

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000592

Gnomad OTH exome AF: 0.00142

GnomAD4 exome AF: 0.000958 AC: 1365 AN: 1424296 Hom.: 30 Cov.: 30 AF XY: 0.000822 AC XY: 582 AN XY: 708100

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000254

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.0108 AC: 1639 AN: 152318 Hom.: 32 Cov.: 32 AF XY: 0.0101 AC XY: 755 AN XY: 74498

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00526 Hom.: 2

Bravo AF: 0.0123

Asia WGS AF: 0.00346 AC: 12 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

Invitae

Dec 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs111710593; hg19: chr15-62147170;