rs3740469

Variant names:

• chr10-104003268-C-G
• rs3740469
• NM_014720.4:c.2090C>G
• SLK p.Thr697Ser

Your query was ambiguous. Multiple possible variants found:

• chr10-104003268-C-G
• chr10-104003268-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014720.4(SLK):​c.2090C>G​(p.Thr697Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T697N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLK NM_014720.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 29 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063029826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014720.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLK	NM_014720.4	MANE Select	c.2090C>G	p.Thr697Ser	missense	Exon 9 of 19	NP_055535.2
	SLK	NM_001304743.2		c.2090C>G	p.Thr697Ser	missense	Exon 9 of 18	NP_001291672.1	Q9H2G2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLK	ENST00000369755.4	TSL:1 MANE Select	c.2090C>G	p.Thr697Ser	missense	Exon 9 of 19	ENSP00000358770.3	Q9H2G2-1
	SLK	ENST00000335753.8	TSL:1	c.2090C>G	p.Thr697Ser	missense	Exon 9 of 18	ENSP00000336824.4	Q9H2G2-2
	SLK	ENST00000946374.1		c.2117C>G	p.Thr706Ser	missense	Exon 9 of 19	ENSP00000616433.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.0
DANN	Benign	0.22
DEOGEN2	Benign	0.0087	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.57	N
PhyloP100		0.29
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.080
Sift	Benign	0.49	T
Sift4G	Benign	0.71	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.023
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3740469;

hg19: chr10-105763026;