rs805657

Variant names:

• chr10-104002833-G-A
• rs805657
• NM_014720.4:c.1655G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014720.4(SLK):​c.1655G>A​(p.Cys552Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,608 control chromosomes in the GnomAD database, including 26,214 homozygotes. 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. C552R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3840 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22374 hom.)
• Consequence: SLK NM_014720.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00410372).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLK	NM_014720.4	c.1655G>A	p.Cys552Tyr	missense_variant	Exon 9 of 19	ENST00000369755.4	NP_055535.2
SLK	NM_001304743.2	c.1655G>A	p.Cys552Tyr	missense_variant	Exon 9 of 18		NP_001291672.1
SLK	XM_011540401.4	c.993+1261G>A		intron_variant	Intron 8 of 17		XP_011538703.1
SLK	XM_047426039.1	c.993+1261G>A		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.1655G>A	p.Cys552Tyr	missense_variant	Exon 9 of 19	1	NM_014720.4	ENSP00000358770.3
SLK	ENST00000335753.8	c.1655G>A	p.Cys552Tyr	missense_variant	Exon 9 of 18	1		ENSP00000336824.4

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32376 AN: 151922 Hom.: 3829 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.183 AC: 46081 AN: 251256 AF XY: 0.181

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.0764

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.172 AC: 251345 AN: 1461568 Hom.: 22374 Cov.: 34 AF XY: 0.172 AC XY: 125223 AN XY: 727058

African (AFR) AF: 0.318 AC: 10638 AN: 33468

American (AMR) AF: 0.201 AC: 8971 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3766 AN: 26130

East Asian (EAS) AF: 0.109 AC: 4346 AN: 39692

South Asian (SAS) AF: 0.176 AC: 15159 AN: 86244

European-Finnish (FIN) AF: 0.229 AC: 12243 AN: 53400

Middle Eastern (MID) AF: 0.152 AC: 879 AN: 5768

European-Non Finnish (NFE) AF: 0.166 AC: 184765 AN: 1111768

Other (OTH) AF: 0.175 AC: 10578 AN: 60388

GnomAD4 genome AF: 0.213 AC: 32433 AN: 152040 Hom.: 3840 Cov.: 32 AF XY: 0.214 AC XY: 15901 AN XY: 74304

African (AFR) AF: 0.316 AC: 13082 AN: 41430

American (AMR) AF: 0.179 AC: 2730 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3472

East Asian (EAS) AF: 0.0952 AC: 493 AN: 5180

South Asian (SAS) AF: 0.176 AC: 850 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2443 AN: 10566

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11640 AN: 67974

Other (OTH) AF: 0.203 AC: 429 AN: 2116

Alfa AF: 0.182 Hom.: 10641

Bravo AF: 0.216

TwinsUK AF: 0.173 AC: 642

ALSPAC AF: 0.163 AC: 629

ESP6500AA AF: 0.309 AC: 1360

ESP6500EA AF: 0.167 AC: 1436

ExAC AF: 0.186 AC: 22542

Asia WGS AF: 0.154 AC: 535 AN: 3478

EpiCase AF: 0.167

EpiControl AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.5
DANN	Benign	0.25
DEOGEN2	Benign	0.0060	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.10	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N
PhyloP100		-0.047
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.036
Sift	Benign	0.29	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.043
MPC		0.064
ClinPred		0.0027	T
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs805657; hg19: chr10-105762591; COSMIC: COSV59824487;