12-27315003-AT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015000.4(STK38L):c.673-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,534,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: STK38L NM_015000.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.120

Genes affected

STK38L (HGNC:17848): (serine/threonine kinase 38 like) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in intracellular signal transduction. Acts upstream of or within protein phosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-27315003-AT-A is Benign according to our data. Variant chr12-27315003-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK38L	NM_015000.4	c.673-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK38L	ENST00000389032.8	c.673-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015000.4	P1
STK38L	ENST00000545470.5	c.550-3del		splice_polypyrimidine_tract_variant, intron_variant		3
STK38L	ENST00000407753.2	c.*147-3del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3
STK38L	ENST00000536093.5	c.97-3del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000529 AC: 8 AN: 151200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000400 AC: 553 AN: 1383404 Hom.: 0 Cov.: 28 AF XY: 0.000379 AC XY: 261 AN XY: 688758

Gnomad4 AFR exome AF: 0.000611

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.000366

Gnomad4 EAS exome AF: 0.000263

Gnomad4 SAS exome AF: 0.000742

Gnomad4 FIN exome AF: 0.000276

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.000350

GnomAD4 genome AF: 0.0000529 AC: 8 AN: 151200 Hom.: 0 Cov.: 32 AF XY: 0.0000678 AC XY: 5 AN XY: 73784

Gnomad4 AFR AF: 0.000146

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00434 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

STK38L-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs759405089; hg19: chr12-27467936;