rs137852559
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4
The NM_000451.4(SHOX):c.877T>C(p.Ter293Argext*?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
SHOX
NM_000451.4 stop_lost
NM_000451.4 stop_lost
Scores
2
2
Clinical Significance
Conservation
PhyloP100: 4.38
Publications
0 publications found
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]
SHOX Gene-Disease associations (from GenCC):
- Langer mesomelic dysplasiaInheritance: AR, XL, Unknown Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
- Leri-Weill dyschondrosteosisInheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, PanelApp Australia
- SHOX-related short statureInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_000451.4 Downstream stopcodon found after 327 codons.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000451.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SHOX | MANE Select | c.877T>C | p.Ter293Argext*? | stop_lost | Exon 5 of 5 | ENSP00000508521.1 | O15266-1 | ||
| SHOX | TSL:1 | c.633+3547T>C | intron | N/A | ENSP00000370987.1 | O15266-2 | |||
| SHOX | TSL:5 | c.877T>C | p.Ter293Argext*? | stop_lost | Exon 6 of 6 | ENSP00000370990.1 | O15266-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1324448Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 652294
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1324448
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
652294
African (AFR)
AF:
AC:
0
AN:
26634
American (AMR)
AF:
AC:
0
AN:
26764
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23102
East Asian (EAS)
AF:
AC:
0
AN:
29654
South Asian (SAS)
AF:
AC:
0
AN:
72818
European-Finnish (FIN)
AF:
AC:
0
AN:
33058
Middle Eastern (MID)
AF:
AC:
0
AN:
3880
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1053586
Other (OTH)
AF:
AC:
0
AN:
54952
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
1
-
Leri-Weill dyschondrosteosis (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
DANN
Benign
FATHMM_MKL
Uncertain
D
PhyloP100
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
Publications
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