rs750375727

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_000451.4(SHOX):c.698C>A(p.Ala233Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,370,048 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A233V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. 1 hem. )

Consequence

SHOX
NM_000451.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.40

Publications

0 publications found

Variant links:

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):

Leri-Weill dyschondrosteosis
Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
Langer mesomelic dysplasia
Inheritance: Unknown, XL, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
SHOX-related short stature
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SHOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 17 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: -0.53811 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia, SHOX-related short stature.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_000451.4 link	c.698C>A	p.Ala233Glu	missense_variant	Exon 5 of 5	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2 link	c.633+3368C>A		intron_variant	Intron 5 of 5		NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SHOX	ENST00000686671.1 link	c.698C>A	p.Ala233Glu	missense_variant	Exon 5 of 5		NM_000451.4	ENSP00000508521.1
SHOX	ENST00000381575.6 link	c.633+3368C>A		intron_variant	Intron 4 of 4	1		ENSP00000370987.1
SHOX	ENST00000381578.6 link	c.698C>A	p.Ala233Glu	missense_variant	Exon 6 of 6	5		ENSP00000370990.1
SHOX	ENST00000334060.8 link	c.633+3368C>A		intron_variant	Intron 5 of 5	5		ENSP00000335505.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000827

AC:

AN:

120878

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000428

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370048

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28784

American (AMR)

AF:

0.00

AC:

AN:

35036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24540

East Asian (EAS)

AF:

0.00

AC:

AN:

33770

South Asian (SAS)

AF:

0.00

AC:

AN:

77452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4262

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074406

Other (OTH)

AF:

0.0000175

AC:

AN:

57170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.79

MetaRNN

Uncertain

0.52

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

1.6

PhyloP100

4.4

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.57

Sift

Benign

0.044

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.28

MutPred

0.27

Gain of catalytic residue at A233 (P = 0.0329);

MVP

0.94

MPC

1.7

ClinPred

0.99

GERP RS

1.7

Varity_R

0.59

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over