rs10492349

Positions:

• chr12-10638229-A-G

Variant summary

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

The NM_018423.3(STYK1):​c.-194-1033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,192 control chromosomes in the GnomAD database, including 3,943 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3943 hom., cov: 32)
• Consequence: STYK1 NM_018423.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYK1	NM_018423.3	c.-194-1033T>C		intron_variant		ENST00000075503.8	NP_060893.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STYK1	ENST00000075503.8	c.-194-1033T>C		intron_variant		1	NM_018423.3	ENSP00000075503	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32683 AN: 152074 Hom.: 3946 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.215 AC: 32681 AN: 152192 Hom.: 3943 Cov.: 32 AF XY: 0.218 AC XY: 16198 AN XY: 74400

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.0943

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.240

Alfa AF: 0.254 Hom.: 2577

Bravo AF: 0.208

Asia WGS AF: 0.151 AC: 523 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.73

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: rs10492349; hg19: chr12-10790828;