chr17-63726643-A-T

Variant names:

• chr17-63726643-A-T
• rs768402945
• ENST00000375840.9:c.-57T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001003788.3(STRADA):​c.-57T>A variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: STRADA NM_001003788.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2977205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRADA	NM_001003787.4	c.89T>A	p.Phe30Tyr	missense_variant	Exon 3 of 13	ENST00000336174.12	NP_001003787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRADA	ENST00000336174.12	c.89T>A	p.Phe30Tyr	missense_variant	Exon 3 of 13	1	NM_001003787.4	ENSP00000336655.6
ENSG00000125695	ENST00000580553.1	n.*127T>A		non_coding_transcript_exon_variant	Exon 3 of 12	5		ENSP00000464100.1
ENSG00000125695	ENST00000580553.1	n.*127T>A		3_prime_UTR_variant	Exon 3 of 12	5		ENSP00000464100.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251314 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135844

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;T;.;D;D;D;D;D;T;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.97	L;L;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.31	N;N;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.14	T;D;.;.;.;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;T;.;.;.;.;.;.;.;.;.
Polyphen		0.92	P;.;.;.;.;.;.;.;.;.;.
Vest4		0.62
MutPred		0.23		Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);.;Gain of phosphorylation at F30 (P = 0.03);Gain of phosphorylation at F30 (P = 0.03);
MVP		0.74
MPC		1.4
ClinPred		0.56	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.53

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: rs768402945; hg19: chr17-61804003;