rs532331878
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001010892.3(RSPH4A):c.492G>A(p.Arg164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
RSPH4A
NM_001010892.3 synonymous
NM_001010892.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.409
Genes affected
RSPH4A (HGNC:21558): (radial spoke head component 4A) This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 6-116617115-G-A is Benign according to our data. Variant chr6-116617115-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.409 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.492G>A | p.Arg164= | synonymous_variant | 1/6 | ENST00000229554.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.492G>A | p.Arg164= | synonymous_variant | 1/6 | 1 | NM_001010892.3 | P1 | |
RSPH4A | ENST00000368581.8 | c.492G>A | p.Arg164= | synonymous_variant | 1/5 | 1 | |||
RSPH4A | ENST00000368580.4 | c.492G>A | p.Arg164= | synonymous_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152198Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251366Hom.: 1 AF XY: 0.0000810 AC XY: 11AN XY: 135840
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727242
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2022 | 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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