Variant 10-104002682-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014720.4(SLK):c.1504G>A(p.Val502Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SLK
NM_014720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

SLK (HGNC:11088): (STE20 like kinase) Enables protein homodimerization activity and protein serine/threonine kinase activity. Involved in several processes, including cytoplasmic microtubule organization; protein autophosphorylation; and regulation of focal adhesion assembly. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SLK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115540475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLK	NM_014720.4 linkuse as main transcript	c.1504G>A	p.Val502Ile	missense_variant	9/19	ENST00000369755.4
SLK	NM_001304743.2 linkuse as main transcript	c.1504G>A	p.Val502Ile	missense_variant	9/18
SLK	XM_011540401.4 linkuse as main transcript	c.993+1110G>A		intron_variant
SLK	XM_047426039.1 linkuse as main transcript	c.993+1110G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLK	ENST00000369755.4 linkuse as main transcript	c.1504G>A	p.Val502Ile	missense_variant	9/19	1	NM_014720.4	P1	Q9H2G2-1
SLK	ENST00000335753.8 linkuse as main transcript	c.1504G>A	p.Val502Ile	missense_variant	9/18	1			Q9H2G2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jan 22, 2024

The c.1504G>A (p.V502I) alteration is located in exon 9 (coding exon 9) of the SLK gene. This alteration results from a G to A substitution at nucleotide position 1504, causing the valine (V) at amino acid position 502 to be replaced by an isoleucine (I). 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

0.076

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.92

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.34

T;T

Polyphen

0.010

B;B

Vest4

0.064

MutPred

0.20

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.66

MPC

0.040

ClinPred

0.40

GERP RS

5.1

Varity_R

0.068

gMVP

0.027

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