11-65535978-C-A

Variant names:

• chr11-65535978-C-A
• NM_020680.4:c.1412C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020680.4(SCYL1):​c.1412C>A​(p.Ala471Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCYL1 NM_020680.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCYL1	NM_020680.4	c.1412C>A	p.Ala471Asp	missense_variant	Exon 11 of 18	ENST00000270176.10	NP_065731.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCYL1	ENST00000270176.10	c.1412C>A	p.Ala471Asp	missense_variant	Exon 11 of 18	1	NM_020680.4	ENSP00000270176.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456492 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;T;.;.;T;.;D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D;D;D
MetaSVM	Benign	-0.35	T
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;D;.;.
Vest4		0.97
MutPred		0.72		Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);Loss of helix (P = 0.028);.;.;
MVP		0.57
MPC		1.4
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.81
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65303449;