12-27297714-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015000.4(STK38L):c.-7C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,603,768 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (10 hom.)
• Consequence: STK38L NM_015000.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.770

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-27297714-C-T is Benign according to our data. Variant chr12-27297714-C-T is described in ClinVar as [Benign]. Clinvar id is 3039732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (913/151978) while in subpopulation AFR AF= 0.0203 (839/41424). AF 95% confidence interval is 0.0191. There are 14 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 909 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK38L	NM_015000.4	c.-7C>T		5_prime_UTR_variant	2/14	ENST00000389032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK38L	ENST00000389032.8	c.-7C>T		5_prime_UTR_variant	2/14	1	NM_015000.4	P1

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 909 AN: 151862 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00148 AC: 365 AN: 246530 Hom.: 7 AF XY: 0.00119 AC XY: 159 AN XY: 133268

Gnomad AFR exome AF: 0.0189

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000221

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000535

Gnomad OTH exome AF: 0.000832

GnomAD4 exome AF: 0.000686 AC: 996 AN: 1451790 Hom.: 10 Cov.: 30 AF XY: 0.000612 AC XY: 442 AN XY: 721758

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000456

Gnomad4 SAS exome AF: 0.0000711

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000813

Gnomad4 OTH exome AF: 0.00153

GnomAD4 genome AF: 0.00601 AC: 913 AN: 151978 Hom.: 14 Cov.: 33 AF XY: 0.00599 AC XY: 445 AN XY: 74258

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00312 Hom.: 1

Bravo AF: 0.00686

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

STK38L-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 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	-0.73
Cadd	Benign	5.3
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs111309830; hg19: chr12-27450647; COSMIC: COSV101198825; COSMIC: COSV101198825;