rs2839536
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_080860.4(RSPH1):c.393G>A(p.Ala131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,613,626 control chromosomes in the GnomAD database, including 125,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 9560 hom., cov: 33)
Exomes 𝑓: 0.39 ( 115763 hom. )
Consequence
RSPH1
NM_080860.4 synonymous
NM_080860.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.39
Genes affected
RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 21-42485777-C-T is Benign according to our data. Variant chr21-42485777-C-T is described in ClinVar as [Benign]. Clinvar id is 227050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.39 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.393G>A | p.Ala131= | synonymous_variant | 5/9 | ENST00000291536.8 | |
RSPH1 | NM_001286506.2 | c.279G>A | p.Ala93= | synonymous_variant | 4/8 | ||
RSPH1 | XM_011529786.2 | c.393G>A | p.Ala131= | synonymous_variant | 5/8 | ||
RSPH1 | XM_005261208.3 | c.186G>A | p.Ala62= | synonymous_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.393G>A | p.Ala131= | synonymous_variant | 5/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.279G>A | p.Ala93= | synonymous_variant | 4/8 | 5 | |||
RSPH1 | ENST00000493019.1 | n.1019G>A | non_coding_transcript_exon_variant | 4/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.326 AC: 49473AN: 151918Hom.: 9559 Cov.: 33
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GnomAD3 exomes AF: 0.382 AC: 96012AN: 251430Hom.: 21163 AF XY: 0.373 AC XY: 50723AN XY: 135892
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GnomAD4 exome AF: 0.389 AC: 568517AN: 1461588Hom.: 115763 Cov.: 42 AF XY: 0.385 AC XY: 279789AN XY: 727122
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GnomAD4 genome ? AF: 0.326 AC: 49492AN: 152038Hom.: 9560 Cov.: 33 AF XY: 0.328 AC XY: 24348AN XY: 74288
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Ala131Ala in exon 5 of RSPH1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 39.3% (3379/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2839536). - |
Primary ciliary dyskinesia 24 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at