Genetic Variant STYK1:p.Ser204Gly (chr12-10629516-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018423.3(STYK1):c.610A>G(p.Ser204Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,613,678 control chromosomes in the GnomAD database, including 299,771 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24900 hom., cov: 32)

Exomes 𝑓: 0.61 ( 274871 hom. )

Consequence

STYK1
NM_018423.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.51

Publications

31 publications found

Variant links:

Genes affected

STYK1 (HGNC:18889): (serine/threonine/tyrosine kinase 1) Receptor protein tyrosine kinases, like STYK1, play important roles in diverse cellular and developmental processes, such as cell proliferation, differentiation, and survival (Liu et al., 2004 [PubMed 15150103]).[supplied by OMIM, Mar 2008]

STYK1 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 (MetaRNN=1.1023769E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STYK1	NM_018423.3 link	c.610A>G	p.Ser204Gly	missense_variant	Exon 6 of 11	ENST00000075503.8	NP_060893.2	Q6J9G0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STYK1	ENST00000075503.8 link	c.610A>G	p.Ser204Gly	missense_variant	Exon 6 of 11	1	NM_018423.3	ENSP00000075503.3		Q6J9G0
STYK1	ENST00000542924.1 link	c.121A>G	p.Ser41Gly	missense_variant	Exon 1 of 2	2		ENSP00000443760.1		H0YGL5

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

84785

AN:

151922

Hom.:

24888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.574

GnomAD2 exomes

AF:

0.634

AC:

159143

AN:

250884

AF XY:

0.632

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.754

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.800

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.610

AC:

891551

AN:

1461638

Hom.:

274871

Cov.:

AF XY:

0.610

AC XY:

443606

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.355

AC:

11872

AN:

33478

American (AMR)

AF:

0.744

AC:

33271

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

16018

AN:

26130

East Asian (EAS)

AF:

0.770

AC:

30559

AN:

39688

South Asian (SAS)

AF:

0.631

AC:

54465

AN:

86248

European-Finnish (FIN)

AF:

0.685

AC:

36571

AN:

53408

Middle Eastern (MID)

AF:

0.589

AC:

3373

AN:

5728

European-Non Finnish (NFE)

AF:

0.602

AC:

668842

AN:

1111884

Other (OTH)

AF:

0.606

AC:

36580

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

20288

40576

60865

81153

101441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.558

AC:

84825

AN:

152040

Hom.:

24900

Cov.:

AF XY:

0.572

AC XY:

42516

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.368

AC:

15256

AN:

41450

American (AMR)

AF:

0.668

AC:

10197

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2164

AN:

3472

East Asian (EAS)

AF:

0.789

AC:

4076

AN:

5164

South Asian (SAS)

AF:

0.640

AC:

3084

AN:

4818

European-Finnish (FIN)

AF:

0.697

AC:

7374

AN:

10580

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.599

AC:

40724

AN:

67964

Other (OTH)

AF:

0.576

AC:

1217

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1826

3652

5478

7304

9130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.585

Hom.:

47326

Bravo

AF:

0.552

TwinsUK

AF:

0.603

AC:

2236

ALSPAC

AF:

0.598

AC:

2306

ESP6500AA

AF:

0.380

AC:

1674

ESP6500EA

AF:

0.589

AC:

5065

ExAC

AF:

0.623

AC:

75579

Asia WGS

AF:

0.695

AC:

2417

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

-0.098

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

MetaRNN

Benign

0.000011

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

3.5

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.15

Sift

Benign

0.62

Sift4G

Benign

0.52

Polyphen

0.0010

Vest4

0.064

MPC

0.22

ClinPred

0.0092

GERP RS

5.6

PromoterAI

-0.0055

Neutral

(source)

Varity_R

0.18

gMVP

0.24

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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12-10629516-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over