X-644647-A-AGCCCCCCGCGC

Position:

• chrX-644647-A-AGCCCCCCGCGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000451.4(SHOX):​c.*16_*26dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,452,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., 44 hem., cov: 33)
  • Exomes 𝑓: 0.000071 (0 hom. 45 hem.)
• Consequence: SHOX NM_000451.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.631

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-644647-A-AGCCCCCCGCGC is Benign according to our data. Variant chrX-644647-A-AGCCCCCCGCGC is described in ClinVar as [Likely_benign]. Clinvar id is 256191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 44 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4	c.*16_*26dup		3_prime_UTR_variant	5/5	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2	c.633+3565_633+3575dup		intron_variant			NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1	c.*16_*26dup		3_prime_UTR_variant	5/5		NM_000451.4	ENSP00000508521	P1
SHOX	ENST00000381575.6	c.633+3565_633+3575dup		intron_variant		1		ENSP00000370987
SHOX	ENST00000381578.6	c.*16_*26dup		3_prime_UTR_variant	6/6	5		ENSP00000370990	P1
SHOX	ENST00000334060.8	c.633+3565_633+3575dup		intron_variant		5		ENSP00000335505

Frequencies

GnomAD3 genomes AF: 0.000592 AC: 90 AN: 152066 Hom.: 0 Cov.: 33 AF XY: 0.000592 AC XY: 44 AN XY: 74278

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000707 AC: 92 AN: 1300776 Hom.: 0 Cov.: 31 AF XY: 0.0000704 AC XY: 45 AN XY: 639442

Gnomad4 AFR exome AF: 0.00166

Gnomad4 AMR exome AF: 0.0000911

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000393

Gnomad4 OTH exome AF: 0.000111

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74396

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.000669

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886038300; hg19: chrX-605382;