Variant rs28474801 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006883.2(SHOX):c.657G>A(p.Pro219Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 384,448 control chromosomes in the GnomAD database, including 83,240 homozygotes. There are 135,716 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37556 hom., 50134 hem., cov: 23)

Exomes 𝑓: 0.61 ( 45684 hom. 85582 hem. )

Consequence

SHOX
NM_006883.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-658808-G-A is Benign according to our data. Variant chrX-658808-G-A is described in ClinVar as [Benign]. Clinvar id is 586580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_006883.2 linkuse as main transcript	c.657G>A	p.Pro219Pro	synonymous_variant	6/6		NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000381575.6 linkuse as main transcript	c.657G>A	p.Pro219Pro	synonymous_variant	5/5	1		ENSP00000370987.1		O15266-2
SHOX	ENST00000334060.8 linkuse as main transcript	c.657G>A	p.Pro219Pro	synonymous_variant	6/6	5		ENSP00000335505.3		O15266-2

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

103690

AN:

147328

Hom.:

37509

Cov.:

AF XY:

0.701

AC XY:

50024

AN XY:

71392

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.710

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.676

GnomAD3 exomes

AF:

0.602

AC:

56209

AN:

93302

Hom.:

17686

AF XY:

0.609

AC XY:

31420

AN XY:

51606

show subpopulations

Gnomad AFR exome

AF:

0.857

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.660

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.612

AC:

145133

AN:

237004

Hom.:

45684

Cov.:

AF XY:

0.622

AC XY:

85582

AN XY:

137582

show subpopulations

Gnomad4 AFR exome

AF:

0.866

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.674

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.704

AC:

103795

AN:

147444

Hom.:

37556

Cov.:

AF XY:

0.701

AC XY:

50134

AN XY:

71512

show subpopulations

Gnomad4 AFR

AF:

0.892

Gnomad4 AMR

AF:

0.630

Gnomad4 ASJ

AF:

0.574

Gnomad4 EAS

AF:

0.734

Gnomad4 SAS

AF:

0.696

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.633

Gnomad4 OTH

AF:

0.677

Bravo

AF:

0.713

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Dec 07, 2017	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jun 06, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 30, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SHOX-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 15, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.46

DANN

Benign

0.63

Splicing

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