rs151009077
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001291867.2(NHS):āc.1965T>Gā(p.Pro655=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,210,018 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00066 ( 0 hom., 19 hem., cov: 23)
Exomes š: 0.000064 ( 0 hom. 26 hem. )
Consequence
NHS
NM_001291867.2 synonymous
NM_001291867.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.612
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 Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant X-17726071-T-G is Benign according to our data. Variant chrX-17726071-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 96633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.612 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 19 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHS | NM_001291867.2 | c.1965T>G | p.Pro655= | synonymous_variant | 7/9 | ENST00000676302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHS | ENST00000676302.1 | c.1965T>G | p.Pro655= | synonymous_variant | 7/9 | NM_001291867.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000662 AC: 74AN: 111736Hom.: 0 Cov.: 23 AF XY: 0.000560 AC XY: 19AN XY: 33914
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GnomAD3 exomes AF: 0.000229 AC: 42AN: 183059Hom.: 1 AF XY: 0.000207 AC XY: 14AN XY: 67559
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GnomAD4 exome AF: 0.0000637 AC: 70AN: 1098229Hom.: 0 Cov.: 33 AF XY: 0.0000715 AC XY: 26AN XY: 363583
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GnomAD4 genome AF: 0.000662 AC: 74AN: 111789Hom.: 0 Cov.: 23 AF XY: 0.000559 AC XY: 19AN XY: 33977
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 05, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 10, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Nance-Horan syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at