3-134185987-T-C

Position:

• chr3-134185987-T-C

Variant summary

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

The NM_002958.4(RYK):​c.1102+2850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,064 control chromosomes in the GnomAD database, including 5,780 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 0.26 (5780 hom., cov: 32)
• Consequence: RYK NM_002958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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]

RYK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYK	NM_002958.4	c.1102+2850A>G		intron_variant		ENST00000623711.4	NP_002949.2
RYK	NM_001005861.3	c.1111+2850A>G		intron_variant			NP_001005861.1
RYK	XR_007095716.1	n.1316+2850A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYK	ENST00000623711.4	c.1102+2850A>G		intron_variant		1	NM_002958.4	ENSP00000485095.1
RYK	ENST00000620660.4	c.1111+2850A>G		intron_variant		1		ENSP00000478721.1
RYK	ENST00000480381.1	n.471+2850A>G		intron_variant		5
RYK	ENST00000486725.1	n.154+2850A>G		intron_variant		2		ENSP00000417836.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39746 AN: 151946 Hom.: 5777 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.262 AC: 39778 AN: 152064 Hom.: 5780 Cov.: 32 AF XY: 0.253 AC XY: 18840 AN XY: 74342

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.239

Alfa AF: 0.204 Hom.: 598

Bravo AF: 0.257

Asia WGS AF: 0.0560 AC: 196 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.88

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: rs6795658; hg19: chr3-133904831;