12-27297738-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_015000.4(STK38L):c.18G>T(p.Gly6=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00474 in 1,613,786 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (146 hom.)
• Consequence: STK38L NM_015000.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.27

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 12-27297738-G-T is Benign according to our data. Variant chr12-27297738-G-T is described in ClinVar as [Benign]. Clinvar id is 786605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK38L	NM_015000.4	c.18G>T	p.Gly6=	synonymous_variant	2/14	ENST00000389032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK38L	ENST00000389032.8	c.18G>T	p.Gly6=	synonymous_variant	2/14	1	NM_015000.4	P1

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3858 AN: 152120 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.00671 AC: 1687 AN: 251308 Hom.: 75 AF XY: 0.00459 AC XY: 624 AN XY: 135838

Gnomad AFR exome AF: 0.0911

Gnomad AMR exome AF: 0.00426

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00260 AC: 3794 AN: 1461548 Hom.: 146 Cov.: 30 AF XY: 0.00220 AC XY: 1601 AN XY: 727064

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.00499

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.0254 AC: 3860 AN: 152238 Hom.: 158 Cov.: 32 AF XY: 0.0237 AC XY: 1761 AN XY: 74440

Gnomad4 AFR AF: 0.0875

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0119 Hom.: 31

Bravo AF: 0.0285

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000328

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2017

- -

STK38L-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	12
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs56140810; hg19: chr12-27450671;