X-630307-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006883.2(SHOX):c.-432-159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 151,264 control chromosomes in the GnomAD database, including 40,026 homozygotes. There are 53,619 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (40026 hom., 53619 hem., cov: 32)
• Consequence: SHOX NM_006883.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-630307-A-G is Benign according to our data. Variant chrX-630307-A-G is described in ClinVar as [Benign]. Clinvar id is 1239870.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-630307-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOX	NM_006883.2	c.-432-159A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOX	ENST00000334060.8	c.-432-159A>G		intron_variant		5
SHOX	ENST00000381578.6	c.-432-159A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 109570 AN: 151142 Hom.: 39999 Cov.: 32 AF XY: 0.726 AC XY: 53536 AN XY: 73748

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.727

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.725 AC: 109649 AN: 151264 Hom.: 40026 Cov.: 32 AF XY: 0.726 AC XY: 53619 AN XY: 73878

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.728

Bravo AF: 0.717

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.0
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs28445092; hg19: chrX-591042;