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GeneBe

rs56163554

chr17-63714097-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_001003787.4(STRADA):c.135G>A(p.Ala45=) 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

2

Clinical Significance

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

Conservation

PhyloP100: 0.242
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 id is 212324.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}. Variant chr17-63714097-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.242 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STRADANM_001003787.4 linkuse as main transcriptc.135G>A p.Ala45= synonymous_variant 5/13 ENST00000336174.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STRADAENST00000336174.12 linkuse as main transcriptc.135G>A p.Ala45= synonymous_variant 5/131 NM_001003787.4 P1Q7RTN6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00175
AC:
266
AN:
151878
Hom.:
1
Cov.:
32
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
GnomAD3 exomes
AF:
0.00257
AC:
646
AN:
251348
Hom.:
3
AF XY:
0.00285
AC XY:
387
AN XY:
135840
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 SAS exome
AF:
0.00657
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.:
12
Cov.:
31
AF XY:
0.00238
AC XY:
1732
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.000897
Gnomad4 AMR exome
AF:
0.00217
Gnomad4 ASJ exome
AF:
0.000995
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00619
Gnomad4 FIN exome
AF:
0.000281
Gnomad4 NFE exome
AF:
0.00212
Gnomad4 OTH exome
AF:
0.00290
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00175
AC:
266
AN:
151996
Hom.:
1
Cov.:
32
AF XY:
0.00180
AC XY:
134
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.000386
Gnomad4 AMR
AF:
0.000787
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00705
Gnomad4 FIN
AF:
0.000666
Gnomad4 NFE
AF:
0.00263
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00231
Hom.:
0
Bravo
AF:
0.00162
Asia WGS
AF:
0.00346
AC:
12
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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024STRADA: BP4, BP7, BS2 -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 15, 2015- -
STRADA-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 20, 2019This 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). -
Polyhydramnios, megalencephaly, and symptomatic epilepsy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
Cadd
Benign
9.4
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56163554; hg19: chr17-61791457; COSMIC: COSV55562080; COSMIC: COSV55562080; API