rs3740469

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T697I) has been classified as Likely benign.

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

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

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=0.063029826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLK	NM_014720.4	c.2090C>G	p.Thr697Ser	missense_variant	Exon 9 of 19	ENST00000369755.4	NP_055535.2
SLK	NM_001304743.2	c.2090C>G	p.Thr697Ser	missense_variant	Exon 9 of 18		NP_001291672.1
SLK	XM_011540401.4	c.993+1696C>G		intron_variant	Intron 8 of 17		XP_011538703.1
SLK	XM_047426039.1	c.993+1696C>G		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	c.2090C>G	p.Thr697Ser	missense_variant	Exon 9 of 19	1	NM_014720.4	ENSP00000358770.3
SLK	ENST00000335753.8	c.2090C>G	p.Thr697Ser	missense_variant	Exon 9 of 18	1		ENSP00000336824.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.57	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.080
Sift	Benign	0.49	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.037	B;B
Vest4		0.045
MutPred		0.082		Loss of glycosylation at T697 (P = 0.0634);Loss of glycosylation at T697 (P = 0.0634);
MVP		0.51
MPC		0.042
ClinPred		0.11	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.023

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

Other links and lift over

dbSNP: rs3740469; hg19: chr10-105763026;