chr3-134250504-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002958.4(RYK):c.151C>T(p.Arg51Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,268,614 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.013 ( 16 hom., cov: 30)
Exomes 𝑓: 0.019 ( 253 hom. )
Consequence
RYK
NM_002958.4 missense
NM_002958.4 missense
Scores
1
3
9
Clinical Significance
Conservation
PhyloP100: -0.204
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004956633).
BP6
?
Variant 3-134250504-G-A is Benign according to our data. Variant chr3-134250504-G-A is described in ClinVar as [Benign]. Clinvar id is 781973.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1965/151492) while in subpopulation NFE AF= 0.0184 (1245/67746). AF 95% confidence interval is 0.0175. There are 16 homozygotes in gnomad4. There are 958 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1964 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYK | NM_002958.4 | c.151C>T | p.Arg51Trp | missense_variant | 1/15 | ENST00000623711.4 | |
RYK | NM_001005861.3 | c.151C>T | p.Arg51Trp | missense_variant | 1/15 | ||
RYK | XR_007095716.1 | n.356C>T | non_coding_transcript_exon_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYK | ENST00000623711.4 | c.151C>T | p.Arg51Trp | missense_variant | 1/15 | 1 | NM_002958.4 | A2 | |
RYK | ENST00000620660.4 | c.151C>T | p.Arg51Trp | missense_variant | 1/15 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0130 AC: 1964AN: 151386Hom.: 16 Cov.: 30
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GnomAD3 exomes AF: 0.0200 AC: 394AN: 19676Hom.: 9 AF XY: 0.0181 AC XY: 224AN XY: 12356
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GnomAD4 exome AF: 0.0194 AC: 21697AN: 1117122Hom.: 253 Cov.: 27 AF XY: 0.0191 AC XY: 10280AN XY: 538526
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GnomAD4 genome ? AF: 0.0130 AC: 1965AN: 151492Hom.: 16 Cov.: 30 AF XY: 0.0129 AC XY: 958AN XY: 74042
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D
Vest4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at