Variant chr1-169854916-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020423.7(SCYL3):c.1361A>G(p.Asp454Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SCYL3
NM_020423.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.964

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]

SCYL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCYL3	NM_020423.7 linkuse as main transcript	c.1361A>G	p.Asp454Gly	missense_variant	12/13	ENST00000367771.11	NP_065156.5	Q8IZE3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCYL3	ENST00000367771.11 linkuse as main transcript	c.1361A>G	p.Asp454Gly	missense_variant	12/13	1	NM_020423.7	ENSP00000356745.5	Q8IZE3-2
SCYL3	ENST00000367770.5 linkuse as main transcript	c.1523A>G	p.Asp508Gly	missense_variant	12/13	1		ENSP00000356744.1	Q8IZE3-1
SCYL3	ENST00000367772.8 linkuse as main transcript	c.1523A>G	p.Asp508Gly	missense_variant	13/14	2		ENSP00000356746.4	Q8IZE3-1
SCYL3	ENST00000423670.1 linkuse as main transcript	c.1361A>G	p.Asp454Gly	missense_variant	12/12	5		ENSP00000407993.1	X6RHX1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248618

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134868

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460428

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726550

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.1523A>G (p.D508G) alteration is located in exon 13 (coding exon 12) of the SCYL3 gene. This alteration results from a A to G substitution at nucleotide position 1523, causing the aspartic acid (D) at amino acid position 508 to be replaced by a glycine (G). 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

0.087

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0066

.;T;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.75

T;.;T;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.052

T;T;T;T

Sift4G

Benign

0.25

T;T;T;.

Polyphen

0.0010

B;B;B;.

Vest4

0.090

MutPred

0.20

.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;

MVP

0.38

MPC

0.26

ClinPred

0.11

GERP RS

2.1

Varity_R

0.086

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: 0

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