rs1556468777
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000451.4(SHOX):c.712_714delinsAG(p.Tyr238SerfsTer2) 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 (★).
Frequency
Genomes: not found (cov: 33)
Consequence
SHOX
NM_000451.4 frameshift
NM_000451.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.54
Genes affected
SHOX (HGNC:10853): (SHOX homeobox) This gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients. This gene is highly conserved across species from mammals to fish to flies. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-644469-TAC-AG is Pathogenic according to our data. Variant chrX-644469-TAC-AG is described in ClinVar as [Pathogenic]. Clinvar id is 448378.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_000451.4 | c.712_714delinsAG | p.Tyr238SerfsTer2 | frameshift_variant | 5/5 | ENST00000686671.1 | |
SHOX | NM_006883.2 | c.633+3382_633+3384delinsAG | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000686671.1 | c.712_714delinsAG | p.Tyr238SerfsTer2 | frameshift_variant | 5/5 | NM_000451.4 | P1 | ||
SHOX | ENST00000381575.6 | c.633+3382_633+3384delinsAG | intron_variant | 1 | |||||
SHOX | ENST00000381578.6 | c.712_714delinsAG | p.Tyr238SerfsTer2 | frameshift_variant | 6/6 | 5 | P1 | ||
SHOX | ENST00000334060.8 | c.633+3382_633+3384delinsAG | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 17, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at