rs1556038355
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001291867.2(NHS):c.1462_1465del(p.Asp488LysfsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
NHS
NM_001291867.2 frameshift
NM_001291867.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
NHS (HGNC:7820): (NHS actin remodeling regulator) This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-17725565-GCAGA-G is Pathogenic according to our data. Variant chrX-17725565-GCAGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 463037.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHS | NM_001291867.2 | c.1462_1465del | p.Asp488LysfsTer10 | frameshift_variant | 7/9 | ENST00000676302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHS | ENST00000676302.1 | c.1462_1465del | p.Asp488LysfsTer10 | frameshift_variant | 7/9 | NM_001291867.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nance-Horan syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2017 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in NHS are known to be pathogenic (PMID: 15623749, 15466011). This sequence change deletes 4 nucleotides from exon 6 of the NHS mRNA (c.1399_1402delGACA), causing a frameshift at codon 467. This creates a premature translational stop signal (p.Asp467Lysfs*10) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at