X-631191-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000451.4(SHOX):c.277+17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,612,446 control chromosomes in the GnomAD database, including 764,790 homozygotes. There are 779,154 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71631 hom., 72226 hem., cov: 34)

Exomes 𝑓: 0.97 ( 693159 hom. 706928 hem. )

Consequence

SHOX
NM_000451.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.909

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-631191-T-G is Benign according to our data. Variant chrX-631191-T-G is described in ClinVar as Benign. ClinVar VariationId is 93092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

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.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOX	NM_000451.4	MANE Select	c.277+17T>G		intron	N/A	NP_000442.1
	SHOX	NM_006883.2		c.277+17T>G		intron	N/A	NP_006874.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SHOX	ENST00000686671.1	MANE Select	c.277+17T>G	intron	N/A	ENSP00000508521.1
SHOX	ENST00000381575.6	TSL:1	c.277+17T>G	intron	N/A	ENSP00000370987.1
SHOX	ENST00000381578.6	TSL:5	c.277+17T>G	intron	N/A	ENSP00000370990.1

Frequencies

GnomAD3 genomes

AF:

0.970

AC:

147558

AN:

152152

Hom.:

71581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.960

Gnomad AMI

AF:

0.988

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.921

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.977

Gnomad OTH

AF:

0.973

GnomAD2 exomes

AF:

0.970

AC:

241076

AN:

248660

AF XY:

0.969

show subpopulations

Gnomad AFR exome

AF:

0.958

Gnomad AMR exome

AF:

0.986

Gnomad ASJ exome

AF:

0.917

Gnomad EAS exome

AF:

0.947

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.976

Gnomad OTH exome

AF:

0.966

GnomAD4 exome

AF:

0.974

AC:

1422506

AN:

1460176

Hom.:

693159

Cov.:

AF XY:

0.973

AC XY:

706928

AN XY:

726360

show subpopulations

African (AFR)

AF:

0.961

AC:

32148

AN:

33470

American (AMR)

AF:

0.986

AC:

44088

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.921

AC:

24073

AN:

26132

East Asian (EAS)

AF:

0.949

AC:

37683

AN:

39696

South Asian (SAS)

AF:

0.951

AC:

82001

AN:

86244

European-Finnish (FIN)

AF:

0.987

AC:

51439

AN:

52122

Middle Eastern (MID)

AF:

0.950

AC:

5424

AN:

5708

European-Non Finnish (NFE)

AF:

0.978

AC:

1087111

AN:

1111746

Other (OTH)

AF:

0.970

AC:

58539

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2079

4159

6238

8318

10397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.970

AC:

147667

AN:

152270

Hom.:

71631

Cov.:

AF XY:

0.970

AC XY:

72226

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.960

AC:

39925

AN:

41590

American (AMR)

AF:

0.975

AC:

14917

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.921

AC:

3195

AN:

3468

East Asian (EAS)

AF:

0.948

AC:

4862

AN:

5126

South Asian (SAS)

AF:

0.953

AC:

4596

AN:

4824

European-Finnish (FIN)

AF:

0.989

AC:

10512

AN:

10626

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.976

AC:

66412

AN:

68012

Other (OTH)

AF:

0.974

AC:

2058

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

237

475

712

950

1187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.969

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 25, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:4

Jul 13, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 06, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leri-Weill dyschondrosteosis

Benign:1

Sep 10, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

(source)

DANN

Benign

0.14

PhyloP100

-0.91

PromoterAI

-0.0018

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over