rs759067813

Variant names:

• chrX-644377-G-A
• rs759067813
• NM_000451.4:c.634-14G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-644377-G-A
• chrX-644377-G-C
• chrX-644377-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000451.4(SHOX):​c.634-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,365,854 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom. 1 hem.)
• Consequence: SHOX NM_000451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• 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):

• Leri-Weill dyschondrosteosis

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Langer mesomelic dysplasia

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX	NM_000451.4	c.634-14G>A		intron_variant	Intron 4 of 4	ENST00000686671.1	NP_000442.1
SHOX	NM_006883.2	c.633+3290G>A		intron_variant	Intron 5 of 5		NP_006874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000686671.1	c.634-14G>A		intron_variant	Intron 4 of 4		NM_000451.4	ENSP00000508521.1
SHOX	ENST00000381575.6	c.633+3290G>A		intron_variant	Intron 4 of 4	1		ENSP00000370987.1
SHOX	ENST00000381578.6	c.634-14G>A		intron_variant	Intron 5 of 5	5		ENSP00000370990.1
SHOX	ENST00000334060.8	c.633+3290G>A		intron_variant	Intron 5 of 5	5		ENSP00000335505.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1365854 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 673980

African (AFR) AF: 0.00 AC: 0 AN: 28838

American (AMR) AF: 0.00 AC: 0 AN: 34340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24438

East Asian (EAS) AF: 0.00 AC: 0 AN: 33474

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 77128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072516

Other (OTH) AF: 0.00 AC: 0 AN: 57018

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0030
DANN	Benign	0.87
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs759067813; hg19: chrX-605112;