rs113313554

Variant names:

• chrX-624523-C-A
• rs113313554
• ENST00000381578.6:c.-512C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-624523-C-A
• chrX-624523-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006883.2(SHOX):​c.-512C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 152,102 control chromosomes in the GnomAD database, including 74 homozygotes. There are 2,048 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (74 hom., 2045 hem., cov: 30)
  • Exomes 𝑓: 0.038 (0 hom. 3 hem.)
• Consequence: SHOX NM_006883.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter P:1 B:5
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Langer mesomelic dysplasia

  Inheritance: AR, XL, Unknown Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leri-Weill dyschondrosteosis

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• SHOX-related short stature

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-624523-C-A is Benign according to our data. Variant chrX-624523-C-A is described in ClinVar as Benign. ClinVar VariationId is 191362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0288 (4383/152024) while in subpopulation AFR AF = 0.0413 (1711/41470). AF 95% confidence interval is 0.0396. There are 74 homozygotes in GnomAd4. There are 2045 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 74 XL,Unknown,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006883.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOX	NM_006883.2		c.-512C>A		5_prime_UTR	Exon 1 of 6	NP_006874.1	O15266-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOX	ENST00000381578.6	TSL:5	c.-512C>A		5_prime_UTR	Exon 1 of 6	ENSP00000370990.1	O15266-1
	SHOX	ENST00000334060.8	TSL:5	c.-512C>A		5_prime_UTR	Exon 1 of 6	ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4384 AN: 151906 Hom.: 73 Cov.: 30

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00789

Gnomad FIN AF: 0.00634

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0385 AC: 3 AN: 78 Hom.: 0 Cov.: 0 AF XY: 0.0536 AC XY: 3 AN XY: 56

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0313 AC: 2 AN: 64

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0288 AC: 4383 AN: 152024 Hom.: 74 Cov.: 30 AF XY: 0.0275 AC XY: 2045 AN XY: 74298

African (AFR) AF: 0.0413 AC: 1711 AN: 41470

American (AMR) AF: 0.0338 AC: 517 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00769 AC: 37 AN: 4812

European-Finnish (FIN) AF: 0.00634 AC: 67 AN: 10574

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.0261 AC: 1776 AN: 67966

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Bravo AF: 0.0321

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	1	SHOX-related short stature (2)
-	-	1	Leri-Weill dyschondrosteosis;C0432230:Langer mesomelic dysplasia syndrome;C1845118:SHOX-related short stature (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SHOX-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.58
PhyloP100		0.020
PromoterAI		0.017	Neutral

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

Other links and lift over

dbSNP: rs113313554; hg19: chrX-585258;