Variant rs805657 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014720.4(SLK):c.1655G>A(p.Cys552Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,608 control chromosomes in the GnomAD database, including 26,214 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3840 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22374 hom. )

Consequence

SLK
NM_014720.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00410372).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLK	NM_014720.4 linkuse as main transcript	c.1655G>A	p.Cys552Tyr	missense_variant	9/19	ENST00000369755.4	NP_055535.2
SLK	NM_001304743.2 linkuse as main transcript	c.1655G>A	p.Cys552Tyr	missense_variant	9/18		NP_001291672.1
SLK	XM_011540401.4 linkuse as main transcript	c.993+1261G>A		intron_variant			XP_011538703.1
SLK	XM_047426039.1 linkuse as main transcript	c.993+1261G>A		intron_variant			XP_047281995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLK	ENST00000369755.4 linkuse as main transcript	c.1655G>A	p.Cys552Tyr	missense_variant	9/19	1	NM_014720.4	ENSP00000358770	P1	Q9H2G2-1
SLK	ENST00000335753.8 linkuse as main transcript	c.1655G>A	p.Cys552Tyr	missense_variant	9/18	1		ENSP00000336824		Q9H2G2-2

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32376

AN:

151922

Hom.:

3829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.183

AC:

46081

AN:

251256

Hom.:

4591

AF XY:

0.181

AC XY:

24573

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0764

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.172

AC:

251345

AN:

1461568

Hom.:

22374

Cov.:

AF XY:

0.172

AC XY:

125223

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.213

AC:

32433

AN:

152040

Hom.:

3840

Cov.:

AF XY:

0.214

AC XY:

15901

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.316

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0952

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.174

Hom.:

6310

Bravo

AF:

0.216

TwinsUK

AF:

0.173

AC:

642

ALSPAC

AF:

0.163

AC:

629

ESP6500AA

AF:

0.309

AC:

1360

ESP6500EA

AF:

0.167

AC:

1436

ExAC

AF:

0.186

AC:

22542

Asia WGS

AF:

0.154

AC:

535

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.5

DANN

Benign

0.25

DEOGEN2

Benign

0.0060

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.10

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.036

Sift

Benign

0.29

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.043

MPC

0.064

ClinPred

0.0027

GERP RS

-3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.015

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over