5-172054563-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005990.4(STK10):c.2652+6G>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,603,658 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (101 hom.)
• Consequence: STK10 NM_005990.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0004068
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.561

Genes affected

STK10 (HGNC:11388): (serine/threonine kinase 10) This gene encodes a member of the Ste20 family of serine/threonine protein kinases, and is similar to several known polo-like kinase kinases. The protein can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. The kinase can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-172054563-C-G is Benign according to our data. Variant chr5-172054563-C-G is described in ClinVar as [Benign]. Clinvar id is 788528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK10	NM_005990.4	c.2652+6G>C		splice_donor_region_variant, intron_variant		ENST00000176763.10
STK10	XM_047417627.1	c.2262+6G>C		splice_donor_region_variant, intron_variant
STK10	XM_047417628.1	c.2103+6G>C		splice_donor_region_variant, intron_variant
STK10	XM_047417629.1	c.1968+6G>C		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK10	ENST00000176763.10	c.2652+6G>C		splice_donor_region_variant, intron_variant		1	NM_005990.4	P1
STK10	ENST00000520476.1	c.470+6G>C		splice_donor_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2839 AN: 152154 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00565 AC: 1369 AN: 242108 Hom.: 49 AF XY: 0.00425 AC XY: 559 AN XY: 131416

Gnomad AFR exome AF: 0.0657

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.00676

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000198

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000681

Gnomad OTH exome AF: 0.00303

GnomAD4 exome AF: 0.00244 AC: 3541 AN: 1451386 Hom.: 101 Cov.: 30 AF XY: 0.00216 AC XY: 1558 AN XY: 722256

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.00498

Gnomad4 ASJ exome AF: 0.00611

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.0000445

Gnomad4 NFE exome AF: 0.000391

Gnomad4 OTH exome AF: 0.00625

GnomAD4 genome AF: 0.0187 AC: 2846 AN: 152272 Hom.: 93 Cov.: 32 AF XY: 0.0176 AC XY: 1309 AN XY: 74450

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00225 Hom.: 1

Bravo AF: 0.0221

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000833

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.9
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.12
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: rs113551500; hg19: chr5-171481567;