rs56400929

Positions:

• chr10-104003151-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000369755.4(SLK):​c.1973C>G​(p.Ala658Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,984 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0094 (17 hom., cov: 32)
  • Exomes 𝑓: 0.012 (119 hom.)
• Consequence: SLK ENST00000369755.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026143491).
• BS2: High AC in GnomAd4 at 1431 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLK	NM_014720.4	c.1973C>G	p.Ala658Gly	missense_variant	9/19	ENST00000369755.4	NP_055535.2
SLK	NM_001304743.2	c.1973C>G	p.Ala658Gly	missense_variant	9/18		NP_001291672.1
SLK	XM_011540401.4	c.993+1579C>G		intron_variant			XP_011538703.1
SLK	XM_047426039.1	c.993+1579C>G		intron_variant			XP_047281995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLK	ENST00000369755.4	c.1973C>G	p.Ala658Gly	missense_variant	9/19	1	NM_014720.4	ENSP00000358770	P1
SLK	ENST00000335753.8	c.1973C>G	p.Ala658Gly	missense_variant	9/18	1		ENSP00000336824

Frequencies

GnomAD3 genomes AF: 0.00942 AC: 1432 AN: 152036 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.0101 AC: 2542 AN: 251424 Hom.: 25 AF XY: 0.0100 AC XY: 1362 AN XY: 135884

Gnomad AFR exome AF: 0.00301

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0323

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0122 AC: 17899 AN: 1461830 Hom.: 119 Cov.: 33 AF XY: 0.0116 AC XY: 8460 AN XY: 727212

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.0335

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.00939

GnomAD4 genome AF: 0.00940 AC: 1431 AN: 152154 Hom.: 17 Cov.: 32 AF XY: 0.00967 AC XY: 719 AN XY: 74380

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00674

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0109 Hom.: 8

Bravo AF: 0.00756

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0123 AC: 106

ExAC AF: 0.0107 AC: 1299

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.91
DANN	Benign	0.45
DEOGEN2	Benign	0.0064	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.15
Sift	Benign	0.27	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0	B;B
Vest4		0.071
MPC		0.044
ClinPred		0.0058	T
GERP RS		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56400929; hg19: chr10-105762909;