X-101837777-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000263032.5(ENSG00000290798):​n.1279+5G>T variant causes a splice region, intron change. 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

ENSG00000290798
ENST00000263032.5 splice_region, intron

Scores

2
Splicing: ADA: 1.000
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91
Variant links:
Genes affected
NXF5 (HGNC:8075): (nuclear RNA export factor 5) This gene is one member of a family of nuclear RNA export factor genes. Most transcript variants are candidates for nonsense-mediated decay (NMD) and may not express proteins in vivo. [provided by RefSeq, Sep 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NXF5NR_028089.1 linkn.1279+5G>T splice_region_variant, intron_variant Intron 14 of 18
NXF5NR_159736.1 linkn.1090+5G>T splice_region_variant, intron_variant Intron 12 of 16
NXF5NR_159737.1 linkn.1090+5G>T splice_region_variant, intron_variant Intron 12 of 16

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000290798ENST00000263032.5 linkn.1279+5G>T splice_region_variant, intron_variant Intron 14 of 18 1
ENSG00000290798ENST00000332614.6 linkn.1090+5G>T splice_region_variant, intron_variant Intron 12 of 16 1
ENSG00000290798ENST00000361330.5 linkn.1090+5G>T splice_region_variant, intron_variant Intron 12 of 16 1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 03, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change falls in intron 14 of the NXF5 gene. It does not directly change the encoded amino acid sequence of the NXF5 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NXF5-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
15
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
1.0
SpliceAI score (max)
0.96
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.96
Position offset: 5

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101092749; API