17-63705560-C-T

Position:

• chr17-63705560-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003787.4(STRADA):​c.859-978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 155,262 control chromosomes in the GnomAD database, including 35,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (35053 hom., cov: 31)
  • Exomes 𝑓: 0.57 (561 hom.)
• Consequence: STRADA NM_001003787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRADA	NM_001003787.4	c.859-978G>A		intron_variant		ENST00000336174.12	NP_001003787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRADA	ENST00000336174.12	c.859-978G>A		intron_variant		1	NM_001003787.4	ENSP00000336655.6
ENSG00000125695	ENST00000580553.1	n.*773-978G>A		intron_variant		5		ENSP00000464100.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100224 AN: 151908 Hom.: 34991 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.623

GnomAD4 exome AF: 0.572 AC: 1850 AN: 3236 Hom.: 561 Cov.: 0 AF XY: 0.579 AC XY: 1011 AN XY: 1746

Gnomad4 AFR exome AF: 0.917

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.660 AC: 100345 AN: 152026 Hom.: 35053 Cov.: 31 AF XY: 0.662 AC XY: 49148 AN XY: 74286

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.622

Alfa AF: 0.572 Hom.: 34892

Bravo AF: 0.670

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.26

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: rs721575; hg19: chr17-61782920;