rs3124

chr10-104029147-A-Cchr10-104029147-A-Gchr10-104029147-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014720.4(SLK):c.*3427A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,148 control chromosomes in the GnomAD database, including 3,706 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3705 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SLK NM_014720.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLK	NM_014720.4	c.*3427A>C		3_prime_UTR_variant	19/19	ENST00000369755.4
SLK	NM_001304743.2	c.*3427A>C		3_prime_UTR_variant	18/18
SLK	XM_011540401.4	c.*3427A>C		3_prime_UTR_variant	18/18
SLK	XM_047426039.1	c.*3427A>C		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLK	ENST00000369755.4	c.*3427A>C		3_prime_UTR_variant	19/19	1	NM_014720.4	P1
SLK	ENST00000335753.8	c.*3427A>C		3_prime_UTR_variant	18/18	1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31810 AN: 152026 Hom.: 3693 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.209 AC: 31874 AN: 152144 Hom.: 3705 Cov.: 32 AF XY: 0.210 AC XY: 15648 AN XY: 74382

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.202

Alfa AF: 0.179 Hom.: 2428

Bravo AF: 0.210

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	8.7
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3124; hg19: chr10-105788905;