NM_020680.4:c.849+242C>A

Variant names:

• chr11-65527359-C-A
• rs1787663
• NM_020680.4:c.849+242C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020680.4(SCYL1):​c.849+242C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,080 control chromosomes in the GnomAD database, including 8,316 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8316 hom., cov: 31)
• Consequence: SCYL1 NM_020680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 21 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, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL1	NM_020680.4	MANE Select	c.849+242C>A		intron	N/A	NP_065731.3
	SCYL1	NM_001425179.1		c.849+242C>A		intron	N/A	NP_001412108.1
	SCYL1	NM_001425180.1		c.846+242C>A		intron	N/A	NP_001412109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCYL1	ENST00000270176.10	TSL:1 MANE Select	c.849+242C>A		intron	N/A	ENSP00000270176.5
	SCYL1	ENST00000420247.6	TSL:1	c.849+242C>A		intron	N/A	ENSP00000408192.2
	SCYL1	ENST00000524944.5	TSL:1	c.849+242C>A		intron	N/A	ENSP00000432175.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47498 AN: 151962 Hom.: 8300 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.313 AC: 47542 AN: 152080 Hom.: 8316 Cov.: 31 AF XY: 0.302 AC XY: 22426 AN XY: 74322

African (AFR) AF: 0.469 AC: 19455 AN: 41446

American (AMR) AF: 0.239 AC: 3646 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1103 AN: 5172

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10590

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18623 AN: 67984

Other (OTH) AF: 0.270 AC: 571 AN: 2114

Alfa AF: 0.286 Hom.: 11732

Bravo AF: 0.331

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.55
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: rs1787663; hg19: chr11-65294830;