rs3759259

chr12-10629516-T-Achr12-10629516-T-Cchr12-10629516-T-G

Variant summary

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

The NM_018423.3(STYK1):c.610A>T(p.Ser204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S204G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STYK1 NM_018423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

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]

ACMG classification

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	UniProt
STYK1	NM_018423.3	c.610A>T	p.Ser204Cys	missense_variant	6/11	ENST00000075503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STYK1	ENST00000075503.8	c.610A>T	p.Ser204Cys	missense_variant	6/11	1	NM_018423.3	P1
STYK1	ENST00000542924.1	c.124A>T	p.Ser42Cys	missense_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.39
Sift	Benign	0.040	D
Sift4G	Uncertain	0.057	T
Polyphen		0.88	P
Vest4		0.37
MutPred		0.58		Gain of catalytic residue at S204 (P = 0.1047);
MVP		0.95
MPC		0.59
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.22
gMVP		0.28

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

Other links and lift over

dbSNP: rs3759259; hg19: chr12-10782115;