Variant 17-63704443-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001003787.4(STRADA):c.998G>T(p.Arg333Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,610,206 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

STRADA
NM_001003787.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.33

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:

Genome browser will be placed here

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/exons	MANE	Protein	UniProt
STRADA	NM_001003787.4 linkuse as main transcript	c.998G>T	p.Arg333Leu	missense_variant	11/13	ENST00000336174.12	NP_001003787.1	Q7RTN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STRADA	ENST00000336174.12 linkuse as main transcript	c.998G>T	p.Arg333Leu	missense_variant	11/13	1	NM_001003787.4	ENSP00000336655.6	Q7RTN6-1
ENSG00000125695	ENST00000580553.1 linkuse as main transcript	n.*912G>T		non_coding_transcript_exon_variant	10/12	5		ENSP00000464100.1	J3QR89
ENSG00000125695	ENST00000580553.1 linkuse as main transcript	n.*912G>T		3_prime_UTR_variant	10/12	5		ENSP00000464100.1	J3QR89

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246506

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134000

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1459300

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

725734

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000234

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150906

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73636

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

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

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.064

MetaRNN

Benign

0.39

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

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.82

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

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.99

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

REVEL

Benign

0.28

Sift

Benign

0.15

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

Sift4G

Benign

0.47

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

Polyphen

0.63, 0.55, 0.43

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

Vest4

0.76, 0.74, 0.73, 0.62, 0.80

MutPred

0.40

.;.;Loss of helix (P = 0.0237);.;.;.;.;.;.;.;.;Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;.;

MVP

0.79

MPC

1.4

ClinPred

0.57

GERP RS

4.9

Varity_R

0.72

gMVP

0.54

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over