Variant 10-104002575-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014720.4(SLK):c.1397A>T(p.Asn466Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,604,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLK
NM_014720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.257

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11614436).

BS2

High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLK	NM_014720.4 linkuse as main transcript	c.1397A>T	p.Asn466Ile	missense_variant	9/19	ENST00000369755.4
SLK	NM_001304743.2 linkuse as main transcript	c.1397A>T	p.Asn466Ile	missense_variant	9/18
SLK	XM_011540401.4 linkuse as main transcript	c.993+1003A>T		intron_variant
SLK	XM_047426039.1 linkuse as main transcript	c.993+1003A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLK	ENST00000369755.4 linkuse as main transcript	c.1397A>T	p.Asn466Ile	missense_variant	9/19	1	NM_014720.4	P1	Q9H2G2-1
SLK	ENST00000335753.8 linkuse as main transcript	c.1397A>T	p.Asn466Ile	missense_variant	9/18	1			Q9H2G2-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

244434

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

132914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1452002

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

722808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 03, 2024

The c.1397A>T (p.N466I) alteration is located in exon 9 (coding exon 9) of the SLK gene. This alteration results from a A to T substitution at nucleotide position 1397, causing the asparagine (N) at amino acid position 466 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

0.074

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.89

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.60

P;P

Vest4

0.13

MutPred

0.18

Gain of methylation at K468 (P = 0.0505);Gain of methylation at K468 (P = 0.0505);

MVP

0.70

MPC

0.051

ClinPred

0.059

GERP RS

-0.89

Varity_R

0.097

gMVP

0.10

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