X-630960-C-T

Position:

chrX-630960-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000451.4(SHOX):c.63C>T(p.Gly21Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00577 in 1,613,250 control chromosomes in the GnomAD database, including 39 homozygotes. There are 4,541 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., 289 hem., cov: 33)

Exomes 𝑓: 0.0059 ( 34 hom. 4252 hem. )

Consequence

SHOX
NM_000451.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.389

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-630960-C-T is Benign according to our data. Variant chrX-630960-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 36776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-630960-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.389 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	1/5	ENST00000686671.1	NP_000442.1	O15266-1A0A024R385
SHOX	NM_006883.2 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	2/6		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SHOX	ENST00000686671.1 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	1/5		NM_000451.4	ENSP00000508521.1	O15266-1
SHOX	ENST00000381575.6 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	1/5	1		ENSP00000370987.1	O15266-2
SHOX	ENST00000381578.6 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	2/6	5		ENSP00000370990.1	O15266-1
SHOX	ENST00000334060.8 linkuse as main transcript	c.63C>T	p.Gly21Gly	synonymous_variant	2/6	5		ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

152140

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

289

AN XY:

74324

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00665

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00425

AC:

1066

AN:

250868

Hom.:

AF XY:

0.00426

AC XY:

578

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.00617

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00594

AC:

8681

AN:

1460992

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

4252

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.000837

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.00597

Gnomad4 NFE exome

AF:

0.00679

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00414

AC:

631

AN:

152258

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00593

Gnomad4 NFE

AF:

0.00665

Gnomad4 OTH

AF:

0.00236

Bravo

AF:

0.00347

EpiCase

AF:

0.00687

EpiControl

AF:

0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 17, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 07, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 21, 2013	- -

Leri-Weill dyschondrosteosis;C0432230:Langer mesomelic dysplasia syndrome;C1845118:SHOX-related short stature

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 16, 2022

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 15, 2021

- -

SHOX-related short stature

Other:1

not provided, no classification provided

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Oct 11, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over