11-65535978-CC-TA

Variant names:

• chr11-65535978-CC-TA
• NM_020680.4:c.1412_1413delCCinsTA
• SCYL1 p.Ala471Val

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1

The NM_020680.4(SCYL1):​c.1412_1413delCCinsTA​(p.Ala471Val) variant causes a missense change. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCYL1 NM_020680.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 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: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_020680.4 (SCYL1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

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.1412_1413delCCinsTA	p.Ala471Val	missense	N/A	NP_065731.3
	SCYL1	NM_001425179.1		c.1412_1413delCCinsTA	p.Ala471Val	missense	N/A	NP_001412108.1
	SCYL1	NM_001425180.1		c.1409_1410delCCinsTA	p.Ala470Val	missense	N/A	NP_001412109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL1	ENST00000270176.10	TSL:1 MANE Select	c.1412_1413delCCinsTA	p.Ala471Val	missense	N/A	ENSP00000270176.5	Q96KG9-1
	SCYL1	ENST00000420247.6	TSL:1	c.1412_1413delCCinsTA	p.Ala471Val	missense	N/A	ENSP00000408192.2	Q96KG9-2
	SCYL1	ENST00000524944.5	TSL:1	c.1412_1413delCCinsTA	p.Ala471Val	missense	N/A	ENSP00000432175.1	E9PS17

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

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: chr11-65303449;