1-169854690-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020423.7(SCYL3):ā€‹c.1587C>Gā€‹(p.Asn529Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,614,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000099 ( 1 hom., cov: 32)
Exomes š‘“: 0.000078 ( 0 hom. )

Consequence

SCYL3
NM_020423.7 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.554
Variant links:
Genes affected
SCYL3 (HGNC:19285): (SCY1 like pseudokinase 3) This gene encodes a protein with a kinase domain and four HEAT repeats. The encoded protein interacts with the C-terminal domain of ezrin, an ERM protein, and may play a role in cell adhesion and migration. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03860858).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCYL3NM_020423.7 linkc.1587C>G p.Asn529Lys missense_variant 12/13 ENST00000367771.11 NP_065156.5 Q8IZE3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCYL3ENST00000367771.11 linkc.1587C>G p.Asn529Lys missense_variant 12/131 NM_020423.7 ENSP00000356745.5 Q8IZE3-2
SCYL3ENST00000367770.5 linkc.1749C>G p.Asn583Lys missense_variant 12/131 ENSP00000356744.1 Q8IZE3-1
SCYL3ENST00000367772.8 linkc.1749C>G p.Asn583Lys missense_variant 13/142 ENSP00000356746.4 Q8IZE3-1
SCYL3ENST00000423670.1 linkc.1587C>G p.Asn529Lys missense_variant 12/125 ENSP00000407993.1 X6RHX1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152110
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
250942
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135600
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
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:
0.0000530
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000780
AC:
114
AN:
1461772
Hom.:
0
Cov.:
34
AF XY:
0.0000701
AC XY:
51
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
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:
0.0000926
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152228
Hom.:
1
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2023The c.1749C>G (p.N583K) alteration is located in exon 13 (coding exon 12) of the SCYL3 gene. This alteration results from a C to G substitution at nucleotide position 1749, causing the asparagine (N) at amino acid position 583 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
2.9
DANN
Benign
0.80
DEOGEN2
Benign
0.0057
.;T;T;.
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.69
T;.;T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.039
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.7
.;L;L;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.053
Sift
Benign
0.042
D;D;D;D
Sift4G
Benign
0.085
T;T;T;.
Polyphen
0.10
B;B;B;.
Vest4
0.090
MutPred
0.38
.;Gain of ubiquitination at N583 (P = 0.0025);Gain of ubiquitination at N583 (P = 0.0025);.;
MVP
0.24
MPC
0.25
ClinPred
0.035
T
GERP RS
-0.15
Varity_R
0.035
gMVP
0.11

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.

Other links and lift over

dbSNP: rs200214247; hg19: chr1-169823831; API