rs56163554

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_001003787.4(STRADA):c.135G>A(p.Ala45Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,312 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 12 hom. )

Consequence

STRADA
NM_001003787.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.242

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

polyhydramnios, megalencephaly, and symptomatic epilepsy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

STRADA links:

ENSG00000125695 (HGNC:):

ENSG00000125695 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 17-63714097-C-T is Benign according to our data. Variant chr17-63714097-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212324.

BP7

Synonymous conserved (PhyloP=0.242 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00175 (266/151996) while in subpopulation SAS AF = 0.00705 (34/4824). AF 95% confidence interval is 0.00518. There are 1 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRADA	NM_001003787.4 link	c.135G>A	p.Ala45Ala	synonymous_variant	Exon 5 of 13	ENST00000336174.12	NP_001003787.1	Q7RTN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STRADA	ENST00000336174.12 link	c.135G>A	p.Ala45Ala	synonymous_variant	Exon 5 of 13	1	NM_001003787.4	ENSP00000336655.6	Q7RTN6-1
ENSG00000125695	ENST00000580553.1 link	n.*173G>A		non_coding_transcript_exon_variant	Exon 5 of 12	5		ENSP00000464100.1	J3QR89
ENSG00000125695	ENST00000580553.1 link	n.*173G>A		3_prime_UTR_variant	Exon 5 of 12	5		ENSP00000464100.1	J3QR89

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

266

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000788

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.000666

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00257

AC:

646

AN:

251348

AF XY:

0.00285

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00282

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00225

AC:

3288

AN:

1461316

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1732

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.000897

AC:

AN:

33460

American (AMR)

AF:

0.00217

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39674

South Asian (SAS)

AF:

0.00619

AC:

534

AN:

86222

European-Finnish (FIN)

AF:

0.000281

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00850

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00212

AC:

2360

AN:

1111640

Other (OTH)

AF:

0.00290

AC:

175

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

155

311

466

622

777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

151996

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41438

American (AMR)

AF:

0.000787

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00705

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000666

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00263

AC:

179

AN:

68002

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00356

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

STRADA: BP4, BP7 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Uncertain:1

Jul 15, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polyhydramnios, megalencephaly, and symptomatic epilepsy

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

STRADA-related disorder

Benign:1

Jun 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

-0.24

CADD

Benign

9.4

(source)

DANN

Benign

0.88

PhyloP100

0.24

PromoterAI

0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=293/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over