rs56400929

Variant names:

• chr10-104003151-C-G
• rs56400929
• NM_014720.4:c.1973C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014720.4(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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0094 (17 hom., cov: 32)
  • Exomes 𝑓: 0.012 (119 hom.)
• Consequence: SLK NM_014720.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 7 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 -8 ACMG points.

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

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.1973C>G	p.Ala658Gly	missense	Exon 9 of 19	NP_055535.2
	SLK	NM_001304743.2		c.1973C>G	p.Ala658Gly	missense	Exon 9 of 18	NP_001291672.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLK	ENST00000369755.4	TSL:1 MANE Select	c.1973C>G	p.Ala658Gly	missense	Exon 9 of 19	ENSP00000358770.3
	SLK	ENST00000335753.8	TSL:1	c.1973C>G	p.Ala658Gly	missense	Exon 9 of 18	ENSP00000336824.4
	SLK	ENST00000946374.1		c.2000C>G	p.Ala667Gly	missense	Exon 9 of 19	ENSP00000616433.1

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

GnomAD2 exomes AF: 0.0101 AC: 2542 AN: 251424 AF XY: 0.0100

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 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

African (AFR) AF: 0.00191 AC: 64 AN: 33480

American (AMR) AF: 0.00367 AC: 164 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86256

European-Finnish (FIN) AF: 0.0335 AC: 1787 AN: 53416

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0137 AC: 15270 AN: 1111976

Other (OTH) AF: 0.00939 AC: 567 AN: 60392

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

African (AFR) AF: 0.00219 AC: 91 AN: 41498

American (AMR) AF: 0.00674 AC: 103 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0319 AC: 338 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 844 AN: 68010

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

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 v4.9

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
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.88
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.15
Sift	Benign	0.27	T
Sift4G	Benign	0.38	T
Polyphen		0.0	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs56400929; hg19: chr10-105762909; COSMIC: COSV104652284;