rs1085307110
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_178554.6(KY):c.51_52insTATCGACATGTGCTGTATCTATCGACAT(p.Val18TyrfsTer56) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
KY
NM_178554.6 frameshift
NM_178554.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.257
Genes affected
KY (HGNC:26576): (kyphoscoliosis peptidase) The protein encoded by this gene belongs to the transglutaminase-like superfamily. The protein is involved in the function, maturation and stabilization of the neuromuscular junction and may be required for normal muscle growth. Mutations in this gene are associated with myopathy, myofibrillar, 7. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-134650909-C-CATGTCGATAGATACAGCACATGTCGATA is Pathogenic according to our data. Variant chr3-134650909-C-CATGTCGATAGATACAGCACATGTCGATA is described in ClinVar as [Pathogenic]. Clinvar id is 402246.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KY | NM_178554.6 | c.51_52insTATCGACATGTGCTGTATCTATCGACAT | p.Val18TyrfsTer56 | frameshift_variant | 1/11 | ENST00000423778.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KY | ENST00000423778.7 | c.51_52insTATCGACATGTGCTGTATCTATCGACAT | p.Val18TyrfsTer56 | frameshift_variant | 1/11 | 5 | NM_178554.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia Pathogenic:1
Pathogenic, no assertion criteria provided | research | The Morris Kahn Laboratory of Human Genetics, Ben-Gurion University of the Negev | Feb 14, 2017 | Variant segregates within affected families with a LOD score of 9.02 , more than 12 patients - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at