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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

29 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.216

AC:

54060

AN:

250854

AF XY:

0.220

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 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

African (AFR)

AF:

0.0871

AC:

2911

AN:

33410

American (AMR)

AF:

0.213

AC:

9497

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

5320

AN:

26114

East Asian (EAS)

AF:

0.131

AC:

5204

AN:

39682

South Asian (SAS)

AF:

0.218

AC:

18811

AN:

86194

European-Finnish (FIN)

AF:

0.240

AC:

12807

AN:

53404

Middle Eastern (MID)

AF:

0.220

AC:

1268

AN:

5768

European-Non Finnish (NFE)

AF:

0.240

AC:

266576

AN:

1111418

Other (OTH)

AF:

0.216

AC:

13023

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

13380

26759

40139

53518

66898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8954

17908

26862

35816

44770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.193

AC:

29395

AN:

152128

Hom.:

3113

Cov.:

AF XY:

0.194

AC XY:

14425

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0961

AC:

3990

AN:

41528

American (AMR)

AF:

0.219

AC:

3352

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

714

AN:

3468

East Asian (EAS)

AF:

0.139

AC:

720

AN:

5168

South Asian (SAS)

AF:

0.220

AC:

1060

AN:

4824

European-Finnish (FIN)

AF:

0.236

AC:

2496

AN:

10574

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16403

AN:

67956

Other (OTH)

AF:

0.201

AC:

424

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1229

2459

3688

4918

6147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.219

Hom.:

8645

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

(source)

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

PhyloP100

0.29

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

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over