NM_020680.4:c.937delG

Variant names:

• chr11-65530714-AG-A
• rs864309664
• NM_020680.4:c.937delG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020680.4(SCYL1):​c.937delG​(p.Val313CysfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCYL1 NM_020680.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.77
• Publications: 2 publications found

Genes affected

SCYL1 (HGNC:14372): (SCY1 like pseudokinase 1) This gene encodes a transcriptional regulator belonging to the SCY1-like family of kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. It activates transcription of the telomerase reverse transcriptase and DNA polymerase beta genes. The protein has been localized to the nucleus, and also to the cytoplasm and centrosomes during mitosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SCYL1 Gene-Disease associations (from GenCC):

• acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-65530714-AG-A is Pathogenic according to our data. Variant chr11-65530714-AG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 218907.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020680.4. 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
	SCYL1	NM_020680.4	MANE Select	c.937delG	p.Val313CysfsTer6	frameshift	Exon 7 of 18	NP_065731.3
	SCYL1	NM_001425179.1		c.937delG	p.Val313CysfsTer6	frameshift	Exon 7 of 18	NP_001412108.1
	SCYL1	NM_001425180.1		c.934delG	p.Val312CysfsTer6	frameshift	Exon 7 of 18	NP_001412109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL1	ENST00000270176.10	TSL:1 MANE Select	c.937delG	p.Val313CysfsTer6	frameshift	Exon 7 of 18	ENSP00000270176.5	Q96KG9-1
	SCYL1	ENST00000420247.6	TSL:1	c.937delG	p.Val313CysfsTer6	frameshift	Exon 7 of 18	ENSP00000408192.2	Q96KG9-2
	SCYL1	ENST00000524944.5	TSL:1	c.937delG	p.Val313CysfsTer6	frameshift	Exon 7 of 17	ENSP00000432175.1	E9PS17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs864309664; hg19: chr11-65298185;