rs137852553
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_000451.4(SHOX):c.597C>G(p.Tyr199Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
SHOX
NM_000451.4 stop_gained
NM_000451.4 stop_gained
Scores
2
1
2
Clinical Significance
Conservation
PhyloP100: -0.528
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 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 14 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-641051-C-G is Pathogenic according to our data. Variant chrX-641051-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 9873.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-641051-C-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOX | NM_000451.4 | c.597C>G | p.Tyr199Ter | stop_gained | 4/5 | ENST00000686671.1 | |
SHOX | NM_006883.2 | c.597C>G | p.Tyr199Ter | stop_gained | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOX | ENST00000686671.1 | c.597C>G | p.Tyr199Ter | stop_gained | 4/5 | NM_000451.4 | P1 | ||
SHOX | ENST00000381575.6 | c.597C>G | p.Tyr199Ter | stop_gained | 4/5 | 1 | |||
SHOX | ENST00000381578.6 | c.597C>G | p.Tyr199Ter | stop_gained | 5/6 | 5 | P1 | ||
SHOX | ENST00000334060.8 | c.597C>G | p.Tyr199Ter | stop_gained | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Leri-Weill dyschondrosteosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1998 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;D;D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at