rs2283679

Positions:

• chrX-631617-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000451.4(SHOX):​c.277+443T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,950 control chromosomes in the GnomAD database, including 40,308 homozygotes. There are 54,112 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.73 (40308 hom., 54112 hem., cov: 33)
• Consequence: SHOX NM_000451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-631617-T-C is Benign according to our data. Variant chrX-631617-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4	c.277+443T>C		intron_variant		ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2	c.277+443T>C		intron_variant			NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1	c.277+443T>C		intron_variant			NM_000451.4	ENSP00000508521	P1
SHOX	ENST00000381575.6	c.277+443T>C		intron_variant		1		ENSP00000370987
SHOX	ENST00000334060.8	c.277+443T>C		intron_variant		5		ENSP00000335505
SHOX	ENST00000381578.6	c.277+443T>C		intron_variant		5		ENSP00000370990	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110352 AN: 151830 Hom.: 40271 Cov.: 33 AF XY: 0.729 AC XY: 54019 AN XY: 74128

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.727 AC: 110441 AN: 151950 Hom.: 40308 Cov.: 33 AF XY: 0.729 AC XY: 54112 AN XY: 74258

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.713

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.12

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

Other links and lift over

dbSNP: rs2283679; hg19: chrX-592352; COSMIC: COSV61861242;