rs374178366

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000451.4(SHOX):​c.633+5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SHOX
NM_000451.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0001460
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.713
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SHOXNM_000451.4 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant ENST00000686671.1 NP_000442.1 O15266-1A0A024R385
SHOXNM_006883.2 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant NP_006874.1 O15266-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHOXENST00000686671.1 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant NM_000451.4 ENSP00000508521.1 O15266-1
SHOXENST00000381575.6 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant 1 ENSP00000370987.1 O15266-2
SHOXENST00000381578.6 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant 5 ENSP00000370990.1 O15266-1
SHOXENST00000334060.8 linkuse as main transcriptc.633+5C>A splice_region_variant, intron_variant 5 ENSP00000335505.3 O15266-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
9.3
DANN
Benign
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00015
dbscSNV1_RF
Benign
0.084
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs374178366; hg19: chrX-601827; API