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Y-630910-A-G

Position:

• chrY-630910-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000711141.1(SHOX):​c.13A>G​(p.Thr5Ala) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov:)
• Consequence: SHOX ENST00000711141.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91

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_1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX_1	NM_000451.4_1	c.13A>G	p.Thr5Ala	missense_variant	1/5
SHOX_1	NM_006883.2_1	c.13A>G	p.Thr5Ala	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000711142.1	c.13A>G	p.Thr5Ala	missense_variant	1/5			ENSP00000518640.1
SHOX	ENST00000711141.1	c.13A>G	p.Thr5Ala	missense_variant	1/5	1		ENSP00000518639.1
SHOX	ENST00000711145.1	c.13A>G	p.Thr5Ala	missense_variant	2/6	5		ENSP00000518642.1
SHOX	ENST00000711143.1	c.13A>G	p.Thr5Ala	missense_variant	2/6	5		ENSP00000518641.1

Frequencies

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

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 24, 2024

Variant summary: SHOX c.13A>G (p.Thr5Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250468 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.13A>G in individuals affected with Leri-Weill Dyschondrosteosis and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
CADD	Uncertain	24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1468114661; hg19: chrY-541645;