Variant 11-65525154-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_020680.4(SCYL1):c.1A>T(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.00000912 in 1,206,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

SCYL1
NM_020680.4 initiator_codon

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.60

Variant links:

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 links:

SCYL1 (HGNC:):

SCYL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-65525154-A-T is Pathogenic according to our data. Variant chr11-65525154-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3381066.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCYL1	NM_020680.4 linkuse as main transcript	c.1A>T	p.Met1?	initiator_codon_variant	1/18	ENST00000270176.10	NP_065731.3	Q96KG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCYL1	ENST00000270176.10 linkuse as main transcript	c.1A>T	p.Met1?	initiator_codon_variant	1/18	1	NM_020680.4	ENSP00000270176.5		Q96KG9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

47812

Hom.:

AF XY:

0.00

AC XY:

AN XY:

26612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000498

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000912

AC:

AN:

1206408

Hom.:

Cov.:

AF XY:

0.00000855

AC XY:

AN XY:

585078

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000982

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Jan 04, 2024

PM2_moderate, PVS1_strong -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.19

T;T;.;.;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Pathogenic

0.94

MetaRNN

Pathogenic

0.99

D;D;D;D;D

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;.;D;D;D

Vest4

0.72

MutPred

0.96

Loss of disorder (P = 0.0709);Loss of disorder (P = 0.0709);Loss of disorder (P = 0.0709);Loss of disorder (P = 0.0709);Loss of disorder (P = 0.0709);

MVP

0.30

ClinPred

1.0

GERP RS

4.0

Varity_R

0.96

gMVP

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over