rs12304656

Positions:

• chr12-10629369-C-G
• chr12-10629369-C-T

Variant summary

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

The NM_018423.3(STYK1):​c.633+124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 973,432 control chromosomes in the GnomAD database, including 906 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 0.048 (566 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (340 hom.)
• Consequence: STYK1 NM_018423.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYK1	NM_018423.3	c.633+124G>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.633+124G>C		intron_variant		1	NM_018423.3	ENSP00000075503	P1
STYK1	ENST00000542924.1	c.164+106G>C		intron_variant		2		ENSP00000443760

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7211 AN: 152072 Hom.: 560 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00713 AC: 5856 AN: 821242 Hom.: 340 AF XY: 0.00659 AC XY: 2758 AN XY: 418572

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.00220

Gnomad4 SAS exome AF: 0.00554

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000883

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0476 AC: 7244 AN: 152190 Hom.: 566 Cov.: 33 AF XY: 0.0473 AC XY: 3523 AN XY: 74416

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0356 Hom.: 39

Bravo AF: 0.0531

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.42

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: rs12304656; hg19: chr12-10781968;