Genetic Variant STRADA:p.Val179Met (chr17-63710537-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003787.4(STRADA):c.535G>A(p.Val179Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STRADA
NM_001003787.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

Variant links:

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]

STRADA links:

ENSG00000125695 (HGNC:):

ENSG00000125695 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRADA	NM_001003787.4 link	c.535G>A	p.Val179Met	missense_variant	Exon 8 of 13	ENST00000336174.12	NP_001003787.1	Q7RTN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRADA	ENST00000336174.12 link	c.535G>A	p.Val179Met	missense_variant	Exon 8 of 13	1	NM_001003787.4	ENSP00000336655.6		Q7RTN6-1
ENSG00000125695	ENST00000580553.1 link	n.*495+191G>A		intron_variant	Intron 7 of 11	5		ENSP00000464100.1		J3QR89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.0082

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Benign

0.88

DEOGEN2

Benign

0.079

.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

D;.;D;.;D;.;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.084

MutationAssessor

Benign

1.9

.;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.1

.;.;N;.;.;N;.;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.038

.;.;D;.;.;T;.;.;D;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.090

.;.;T;T;.;T;.;.;T;T;.;.;.;.;.;.;.;T;T;.;.;.;.;.;T;.;.;.;.

Polyphen

0.90, 0.92, 0.99, 0.28

.;P;P;D;P;.;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.

Vest4

0.42, 0.41, 0.42, 0.43, 0.40, 0.41

MutPred

0.57

.;.;Loss of catalytic residue at V179 (P = 0.0621);.;.;.;.;.;.;.;.;Loss of catalytic residue at V179 (P = 0.0621);.;Loss of catalytic residue at V179 (P = 0.0621);Loss of catalytic residue at V179 (P = 0.0621);Loss of catalytic residue at V179 (P = 0.0621);Loss of catalytic residue at V179 (P = 0.0621);.;.;Loss of catalytic residue at V179 (P = 0.0621);.;Loss of catalytic residue at V179 (P = 0.0621);.;.;.;.;.;.;Loss of catalytic residue at V179 (P = 0.0621);

MVP

0.85

MPC

0.45

ClinPred

0.72

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over