15-61854478-GAG-TAA

Variant names:

• chr15-61854478-GAG-TAA
• NM_020821.3:c.11239_11241delCTCinsTTA
• VPS13C p.3748

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_020821.3(VPS13C):​c.11239_11241delCTCinsTTA​(p.3748) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3747L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS13C NM_020821.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.

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.11239_11241delCTCinsTTA	p.3748	synonymous	N/A	NP_065872.1	Q709C8-1
	VPS13C	NM_017684.5		c.11110_11112delCTCinsTTA	p.3705	synonymous	N/A	NP_060154.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13C	ENST00000644861.2	MANE Select	c.11239_11241delCTCinsTTA	p.3748	synonymous	N/A	ENSP00000493560.2	Q709C8-1
	VPS13C	ENST00000249837.7	TSL:1	c.11110_11112delCTCinsTTA	p.3705	synonymous	N/A	ENSP00000249837.3	Q709C8-3
	VPS13C	ENST00000560637.5	TSL:1	n.1608_1610delCTCinsTTA		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-62146677;