Variant 10-104002671-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000369755.4(SLK):c.1493C>T(p.Thr498Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLK
ENST00000369755.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055621028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLK	NM_014720.4 linkuse as main transcript	c.1493C>T	p.Thr498Ile	missense_variant	9/19	ENST00000369755.4	NP_055535.2
SLK	NM_001304743.2 linkuse as main transcript	c.1493C>T	p.Thr498Ile	missense_variant	9/18		NP_001291672.1
SLK	XM_011540401.4 linkuse as main transcript	c.993+1099C>T		intron_variant			XP_011538703.1
SLK	XM_047426039.1 linkuse as main transcript	c.993+1099C>T		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.1493C>T	p.Thr498Ile	missense_variant	9/19	1	NM_014720.4	ENSP00000358770	P1	Q9H2G2-1
SLK	ENST00000335753.8 linkuse as main transcript	c.1493C>T	p.Thr498Ile	missense_variant	9/18	1		ENSP00000336824		Q9H2G2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457826

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725374

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 15, 2023

The c.1493C>T (p.T498I) alteration is located in exon 9 (coding exon 9) of the SLK gene. This alteration results from a C to T substitution at nucleotide position 1493, causing the threonine (T) at amino acid position 498 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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.043

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.0070

B;B

Vest4

0.081

MutPred

0.19

Loss of phosphorylation at T498 (P = 0.0579);Loss of phosphorylation at T498 (P = 0.0579);

MVP

0.53

MPC

0.046

ClinPred

0.039

GERP RS

1.9

Varity_R

0.049

gMVP

0.076

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over