12-10629516-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018423.3(STYK1):​c.610A>C​(p.Ser204Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3632413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STYK1	NM_018423.3	c.610A>C	p.Ser204Arg	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>C	p.Ser204Arg	missense_variant	Exon 6 of 11	1	NM_018423.3	ENSP00000075503.3
STYK1	ENST00000542924.1	c.121A>C	p.Ser41Arg	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	Uncertain	0.35
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.058
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Benign	0.49	T
Polyphen		0.044	B
Vest4		0.45
MutPred		0.58		Gain of solvent accessibility (P = 0.0766);
MVP		0.88
MPC		0.39
ClinPred		0.65	D
GERP RS		5.6
PromoterAI		-0.011	Neutral
Varity_R		0.26
gMVP		0.48
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs3759259; hg19: chr12-10782115;