Genetic Variant SLK:p.Thr697Ile (chr10-104003268-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014720.4(SLK):c.2090C>T(p.Thr697Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,100 control chromosomes in the GnomAD database, including 42,327 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3113 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39214 hom. )

Consequence

SLK
NM_014720.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.287

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=0.0039060116).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLK	NM_014720.4 link	c.2090C>T	p.Thr697Ile	missense_variant	Exon 9 of 19	ENST00000369755.4	NP_055535.2	Q9H2G2-1
SLK	NM_001304743.2 link	c.2090C>T	p.Thr697Ile	missense_variant	Exon 9 of 18		NP_001291672.1	Q9H2G2-2
SLK	XM_011540401.4 link	c.993+1696C>T		intron_variant	Intron 8 of 17		XP_011538703.1
SLK	XM_047426039.1 link	c.993+1696C>T		intron_variant	Intron 8 of 16		XP_047281995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLK	ENST00000369755.4 link	c.2090C>T	p.Thr697Ile	missense_variant	Exon 9 of 19	1	NM_014720.4	ENSP00000358770.3		Q9H2G2-1
SLK	ENST00000335753.8 link	c.2090C>T	p.Thr697Ile	missense_variant	Exon 9 of 18	1		ENSP00000336824.4		Q9H2G2-2

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29390

AN:

152008

Hom.:

3112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0960

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.200

GnomAD3 exomes

AF:

0.216

AC:

54060

AN:

250854

Hom.:

6092

AF XY:

0.220

AC XY:

29768

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.0917

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.230

AC:

335417

AN:

1460972

Hom.:

39214

Cov.:

AF XY:

0.230

AC XY:

166871

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0871

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.193

AC:

29395

AN:

152128

Hom.:

3113

Cov.:

AF XY:

0.194

AC XY:

14425

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.241

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.228

Hom.:

6828

Bravo

AF:

0.186

TwinsUK

AF:

0.244

AC:

906

ALSPAC

AF:

0.258

AC:

994

ESP6500AA

AF:

0.107

AC:

470

ESP6500EA

AF:

0.240

AC:

2065

ExAC

AF:

0.216

AC:

26195

Asia WGS

AF:

0.166

AC:

579

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.65

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.13

Sift

Benign

0.037

D;D

Sift4G

Benign

0.21

T;T

Polyphen

0.0030

B;B

Vest4

0.043

MPC

0.046

ClinPred

0.0083

GERP RS

3.5

Varity_R

0.047

gMVP

0.046

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