Variant chr15-61907381-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020821.3(VPS13C):c.8988A>T(p.Pro2996Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,738 control chromosomes in the GnomAD database, including 1,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 359 hom., cov: 32)

Exomes 𝑓: 0.029 ( 900 hom. )

Consequence

VPS13C
NM_020821.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.339

Variant links:

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 links:

VPS13C (HGNC:):

VPS13C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 15-61907381-T-A is Benign according to our data. Variant chr15-61907381-T-A is described in ClinVar as [Benign]. Clinvar id is 1288720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13C	NM_020821.3 linkuse as main transcript	c.8988A>T	p.Pro2996Pro	synonymous_variant	66/85	ENST00000644861.2	NP_065872.1	Q709C8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13C	ENST00000644861.2 linkuse as main transcript	c.8988A>T	p.Pro2996Pro	synonymous_variant	66/85		NM_020821.3	ENSP00000493560.2		Q709C8-1

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7934

AN:

152196

Hom.:

359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0339

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0245

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0347

AC:

8711

AN:

250960

Hom.:

257

AF XY:

0.0319

AC XY:

4326

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.0327

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.0967

Gnomad SAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0241

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0285

AC:

41664

AN:

1461424

Hom.:

900

Cov.:

AF XY:

0.0279

AC XY:

20284

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0995

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0317

GnomAD4 genome

AF:

0.0521

AC:

7939

AN:

152314

Hom.:

359

Cov.:

AF XY:

0.0510

AC XY:

3800

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0339

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.0866

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.0245

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0576

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

VPS13C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

DANN

Benign

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over