12-10629516-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (24900 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274871 hom.)
• 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 Benign. Variant got -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/exons	MANE	UniProt
STYK1	NM_018423.3	c.610A>G	p.Ser204Gly	missense_variant	6/11	ENST00000075503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STYK1	ENST00000075503.8	c.610A>G	p.Ser204Gly	missense_variant	6/11	1	NM_018423.3	P1
STYK1	ENST00000542924.1	c.124A>G	p.Ser42Gly	missense_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84785 AN: 151922 Hom.: 24888 Cov.: 32

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

GnomAD3 exomes AF: 0.634 AC: 159143 AN: 250884 Hom.: 51898 AF XY: 0.632 AC XY: 85737 AN XY: 135608

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 SAS exome AF: 0.630

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.: 67 AF XY: 0.610 AC XY: 443606 AN XY: 727108

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.744

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.770

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.558 AC: 84825 AN: 152040 Hom.: 24900 Cov.: 32 AF XY: 0.572 AC XY: 42516 AN XY: 74336

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.576

Alfa AF: 0.586 Hom.: 32042

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	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	20
Dann	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.15
Sift	Benign	0.62	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.064
MPC		0.22
ClinPred		0.0092	T
GERP RS		5.6
Varity_R		0.18
gMVP		0.24

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

Other links and lift over

dbSNP: rs3759259; hg19: chr12-10782115; COSMIC: COSV50013940; COSMIC: COSV50013940;