Variant 10-104003151-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014720.4(SLK):c.1973C>G(p.Ala658Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,984 control chromosomes in the GnomAD database, including 136 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 0.0094 ( 17 hom., cov: 32)

Exomes 𝑓: 0.012 ( 119 hom. )

Consequence

SLK
NM_014720.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.878

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026143491).

BS2

High AC in GnomAd4 at 1431 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLK	NM_014720.4 linkuse as main transcript	c.1973C>G	p.Ala658Gly	missense_variant	9/19	ENST00000369755.4	NP_055535.2	Q9H2G2-1
SLK	NM_001304743.2 linkuse as main transcript	c.1973C>G	p.Ala658Gly	missense_variant	9/18		NP_001291672.1	Q9H2G2-2
SLK	XM_011540401.4 linkuse as main transcript	c.993+1579C>G		intron_variant			XP_011538703.1
SLK	XM_047426039.1 linkuse as main transcript	c.993+1579C>G		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.1973C>G	p.Ala658Gly	missense_variant	9/19	1	NM_014720.4	ENSP00000358770.3		Q9H2G2-1
SLK	ENST00000335753.8 linkuse as main transcript	c.1973C>G	p.Ala658Gly	missense_variant	9/18	1		ENSP00000336824.4		Q9H2G2-2

Frequencies

GnomAD3 genomes

AF:

0.00942

AC:

1432

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.00675

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0101

AC:

2542

AN:

251424

Hom.:

AF XY:

0.0100

AC XY:

1362

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0122

AC:

17899

AN:

1461830

Hom.:

119

Cov.:

AF XY:

0.0116

AC XY:

8460

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.0335

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.00939

GnomAD4 genome

AF:

0.00940

AC:

1431

AN:

152154

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

719

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00674

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0319

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00756

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0107

AC:

1299

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.91

DANN

Benign

0.45

DEOGEN2

Benign

0.0064

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.15

Sift

Benign

0.27

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.071

MPC

0.044

ClinPred

0.0058

GERP RS

-8.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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