rs4968596

Positions:

• chr17-63728319-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001003787.4(STRADA):​c.36+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,612,884 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (57 hom.)
• Consequence: STRADA NM_001003787.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.167

Genes affected

STRADA (HGNC:30172): (STE20 related adaptor alpha) The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]

ENSG00000125695 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 17-63728319-T-C is Benign according to our data. Variant chr17-63728319-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00452 (688/152180) while in subpopulation AMR AF= 0.0147 (225/15272). AF 95% confidence interval is 0.0132. There are 8 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRADA	NM_001003787.4	c.36+15A>G		intron_variant		ENST00000336174.12	NP_001003787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRADA	ENST00000336174.12	c.36+15A>G		intron_variant		1	NM_001003787.4	ENSP00000336655.6
ENSG00000125695	ENST00000580553.1	n.*74+15A>G		intron_variant		5		ENSP00000464100.1

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 687 AN: 152062 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00812 AC: 2033 AN: 250284 Hom.: 35 AF XY: 0.00674 AC XY: 912 AN XY: 135356

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.0318

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.00993

Gnomad SAS exome AF: 0.000426

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.000353

Gnomad OTH exome AF: 0.00524

GnomAD4 exome AF: 0.00253 AC: 3692 AN: 1460704 Hom.: 57 Cov.: 30 AF XY: 0.00230 AC XY: 1674 AN XY: 726708

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.0174

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.0267

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00452 AC: 688 AN: 152180 Hom.: 8 Cov.: 32 AF XY: 0.00624 AC XY: 464 AN XY: 74406

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.00389

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Feb 16, 2017

- -

Polyhydramnios, megalencephaly, and symptomatic epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4968596; hg19: chr17-61805679;