12-10629516-T-A

Variant names:

• chr12-10629516-T-A
• rs3759259
• NM_018423.3:c.610A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STYK1 NM_018423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 31 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STYK1	NM_018423.3	c.610A>T	p.Ser204Cys	missense_variant	Exon 6 of 11	ENST00000075503.8	NP_060893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STYK1	ENST00000075503.8	c.610A>T	p.Ser204Cys	missense_variant	Exon 6 of 11	1	NM_018423.3	ENSP00000075503.3
STYK1	ENST00000542924.1	c.121A>T	p.Ser41Cys	missense_variant	Exon 1 of 2	2		ENSP00000443760.1

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
PhyloP100		3.5
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
PromoterAI		-0.0065	Neutral
Varity_R		0.22
gMVP		0.28
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs3759259; hg19: chr12-10782115;