Genetic Variant ENST00000711145.1:c.-507G>C (chrY-624528-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The ENST00000711145.1(SHOX):c.-507G>C 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 Benign (★★).

Frequency

Genomes: not found (cov: )

Consequence

SHOX
ENST00000711145.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: -0.202

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=0.404).

BP6

Variant Y-624528-G-C is Benign according to our data. Variant chrY-624528-G-C is described in ClinVar as [Benign]. Clinvar id is 191361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOX_1	NM_006883.2_1 link	c.-507G>C		5_prime_UTR_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX	ENST00000711145.1 link	c.-507G>C		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000518642.1
SHOX	ENST00000711143.1 link	c.-507G>C		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:

0.302

Hom.:

875

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SHOX-related short stature

Pathogenic:1Benign:1

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.-507G>C in the gene SHOX has an allele frequency of 0.327 in East Asian subpopulation in the gnomAD database, including 1343 homozygous occurrences. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1. -

Genetics Research Lab, Taif University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: not provided

- -

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Leri-Weill dyschondrosteosis

Benign:1

Dec 18, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder

Benign:1

Apr 15, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.40

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over