chrX-17375806-CGGCG-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001291867.2(NHS):c.50_53del(p.Arg17ProfsTer178) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
NHS
NM_001291867.2 frameshift
NM_001291867.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.94
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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 25 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-17375806-CGGCG-C is Pathogenic according to our data. Variant chrX-17375806-CGGCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 1446464.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.50_53del | p.Arg17ProfsTer178 | frameshift_variant | 1/9 | ENST00000676302.1 | |
NHS | NM_198270.4 | c.50_53del | p.Arg17ProfsTer178 | frameshift_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHS | ENST00000676302.1 | c.50_53del | p.Arg17ProfsTer178 | frameshift_variant | 1/9 | NM_001291867.2 | P4 | ||
NHS | ENST00000380060.7 | c.50_53del | p.Arg17ProfsTer178 | frameshift_variant | 1/8 | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
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 | Oct 25, 2020 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with NHS-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Arg17Profs*178) in the NHS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NHS are known to be pathogenic (PMID: 14564667, 19414485). - |
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
Publications
No publications associated with this variant yet.