chr12-10653686-T-C

Position:

• chr12-10653686-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.-194-16490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,084 control chromosomes in the GnomAD database, including 9,159 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 0.33 (9159 hom., cov: 32)
• Consequence: STYK1 NM_018423.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STYK1	NM_018423.3	c.-194-16490A>G		intron_variant		ENST00000075503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STYK1	ENST00000075503.8	c.-194-16490A>G		intron_variant		1	NM_018423.3	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49888 AN: 151966 Hom.: 9161 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.328 AC: 49896 AN: 152084 Hom.: 9159 Cov.: 32 AF XY: 0.319 AC XY: 23752 AN XY: 74342

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.345

Alfa AF: 0.401 Hom.: 7426

Bravo AF: 0.313

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.46

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: rs2418087; hg19: chr12-10806285;