ENST00000381575.6:c.657G>C

Variant names:

• chrX-658808-G-C
• rs28474801
• ENST00000381575.6:c.657G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The ENST00000381575.6(SHOX):​c.657G>C​(p.Pro219Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P219P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SHOX ENST00000381575.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• Leri-Weill dyschondrosteosis

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381575.6. 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.657G>C	p.Pro219Pro	synonymous	Exon 6 of 6	NP_006874.1	O15266-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOX	ENST00000381575.6	TSL:1	c.657G>C	p.Pro219Pro	synonymous	Exon 5 of 5	ENSP00000370987.1	O15266-2
	SHOX	ENST00000334060.8	TSL:5	c.657G>C	p.Pro219Pro	synonymous	Exon 6 of 6	ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 244546 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 141878

African (AFR) AF: 0.00 AC: 0 AN: 5336

American (AMR) AF: 0.00 AC: 0 AN: 22836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9212

East Asian (EAS) AF: 0.00 AC: 0 AN: 5998

South Asian (SAS) AF: 0.00 AC: 0 AN: 49030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 854

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 129224

Other (OTH) AF: 0.00 AC: 0 AN: 11120

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147620 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 71606

African (AFR) AF: 0.00 AC: 0 AN: 40190

American (AMR) AF: 0.00 AC: 0 AN: 14732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4884

South Asian (SAS) AF: 0.00 AC: 0 AN: 4636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67178

Other (OTH) AF: 0.00 AC: 0 AN: 2036

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.44
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs28474801; hg19: chrX-619543;