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ENST00000711145.1:c.-512C>A

Variant names:

• chrY-624523-C-A
• rs113313554
• ENST00000711145.1:c.-512C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000711145.1(SHOX):​c.-512C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov:)
• Consequence: SHOX ENST00000711145.1 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 B:4
• Conservation: PhyloP100: 0.0110

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=5.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX_1	NM_006883.2_1	c.-512C>A		5_prime_UTR_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000711145.1	c.-512C>A		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000518642.1
SHOX	ENST00000711143.1	c.-512C>A		5_prime_UTR_variant	Exon 1 of 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.

Alfa AF: 0.00419 Hom.: 0

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Benign:4

Revision: no assertion criteria provided

Submissions by phenotype

SHOX-related short stature Pathogenic:1 Benign:1

-

Genetics Research Lab, Taif University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: not provided

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

NM_000451.3:c.-512C>A in SHOX gene has an allele frequency of 0.042 in African subpopulation in the gnomAD database, including 15 homozygous occurrences. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2. -

not specified Benign:1

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

SHOX-related disorder Benign:1

May 19, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	5.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113313554; hg19: chrY-535258;