rs398124609
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_001291867.2(NHS):c.4428_4430dup(p.Ser1479dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,209,646 control chromosomes in the GnomAD database, including 1 homozygotes. There are 58 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 3 hem., cov: 22)
Exomes 𝑓: 0.000079 ( 1 hom. 55 hem. )
Consequence
NHS
NM_001291867.2 inframe_insertion
NM_001291867.2 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.55
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 Likely_benign. Variant got -5 ACMG points.
BP6
?
Variant X-17731933-C-CAGT is Benign according to our data. Variant chrX-17731933-C-CAGT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 96642.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}.
BS2
?
High Hemizygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHS | NM_001291867.2 | c.4428_4430dup | p.Ser1479dup | inframe_insertion | 9/9 | ENST00000676302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHS | ENST00000676302.1 | c.4428_4430dup | p.Ser1479dup | inframe_insertion | 9/9 | NM_001291867.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000269 AC: 3AN: 111631Hom.: 0 Cov.: 22 AF XY: 0.0000888 AC XY: 3AN XY: 33799
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GnomAD3 exomes AF: 0.000115 AC: 21AN: 183185Hom.: 0 AF XY: 0.000266 AC XY: 18AN XY: 67657
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GnomAD4 exome AF: 0.0000792 AC: 87AN: 1097957Hom.: 1 Cov.: 31 AF XY: 0.000151 AC XY: 55AN XY: 363331
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GnomAD4 genome ? AF: 0.0000269 AC: 3AN: 111689Hom.: 0 Cov.: 22 AF XY: 0.0000886 AC XY: 3AN XY: 33867
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 30, 2013 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 04, 2020 | - - |
Nance-Horan syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 23, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at