rs13067800

Positions:

• chr3-134153566-T-C

Variant summary

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

The ENST00000484106.3(RYK):​c.435+22043A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,280 control chromosomes in the GnomAD database, including 181 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 0.042 (181 hom., cov: 32)
• Consequence: RYK ENST00000484106.3 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

Genes affected

RYK (HGNC:10481): (receptor like tyrosine kinase) The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. The encoded protein has a leucine-rich extracellular domain with a WIF-type Wnt binding region, a single transmembrane domain, and an intracellular tyrosine kinase domain. This protein is involved in stimulating Wnt signaling pathways such as the regulation of axon pathfinding. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYK	ENST00000484106.3	c.435+22043A>G		intron_variant, NMD_transcript_variant		5		ENSP00000487023

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6421 AN: 152162 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0421 AC: 6418 AN: 152280 Hom.: 181 Cov.: 32 AF XY: 0.0410 AC XY: 3050 AN XY: 74470

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0579 Hom.: 382

Bravo AF: 0.0385

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13067800; hg19: chr3-133872410;