NM_020821.3:c.11077-54A>T

Variant names:

• chr15-61855008-T-A
• rs2241492
• NM_020821.3:c.11077-54A>T

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.11077-54A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,469,650 control chromosomes in the GnomAD database, including 106,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9794 hom., cov: 32)
  • Exomes 𝑓: 0.38 (96473 hom.)
• Consequence: VPS13C NM_020821.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.02
• Publications: 7 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.83).
• BP6: Variant 15-61855008-T-A is Benign according to our data. Variant chr15-61855008-T-A is described in ClinVar as Benign. ClinVar VariationId is 1283776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 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.11077-54A>T		intron	N/A	NP_065872.1	Q709C8-1
	VPS13C	NM_017684.5		c.10948-54A>T		intron	N/A	NP_060154.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	ENST00000644861.2	MANE Select	c.11077-54A>T		intron	N/A	ENSP00000493560.2	Q709C8-1
	VPS13C	ENST00000249837.7	TSL:1	c.10948-54A>T		intron	N/A	ENSP00000249837.3	Q709C8-3
	VPS13C	ENST00000560637.5	TSL:1	n.1446-54A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53867 AN: 151802 Hom.: 9785 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.382 AC: 503194 AN: 1317730 Hom.: 96473 AF XY: 0.382 AC XY: 249651 AN XY: 653820

African (AFR) AF: 0.283 AC: 8226 AN: 29116

American (AMR) AF: 0.463 AC: 12254 AN: 26478

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 7679 AN: 21782

East Asian (EAS) AF: 0.274 AC: 10434 AN: 38036

South Asian (SAS) AF: 0.382 AC: 27547 AN: 72042

European-Finnish (FIN) AF: 0.423 AC: 21157 AN: 50010

Middle Eastern (MID) AF: 0.334 AC: 1707 AN: 5110

European-Non Finnish (NFE) AF: 0.386 AC: 393754 AN: 1020436

Other (OTH) AF: 0.373 AC: 20436 AN: 54720

GnomAD4 genome AF: 0.355 AC: 53897 AN: 151920 Hom.: 9794 Cov.: 32 AF XY: 0.355 AC XY: 26323 AN XY: 74252

African (AFR) AF: 0.282 AC: 11674 AN: 41392

American (AMR) AF: 0.423 AC: 6466 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1187 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1400 AN: 5164

South Asian (SAS) AF: 0.377 AC: 1812 AN: 4812

European-Finnish (FIN) AF: 0.406 AC: 4282 AN: 10552

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25891 AN: 67944

Other (OTH) AF: 0.371 AC: 783 AN: 2110

Alfa AF: 0.273 Hom.: 775

Bravo AF: 0.354

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		-2.0
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: rs2241492; hg19: chr15-62147207; COSMIC: COSV51424088; COSMIC: COSV51424088;