rs533664718
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000229554.10(RSPH4A):c.1536G>A(p.Glu512=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,612,498 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 6 hom. )
Consequence
RSPH4A
ENST00000229554.10 synonymous
ENST00000229554.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0880
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 6-116628243-G-A is Benign according to our data. Variant chr6-116628243-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 525574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.088 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.1536G>A | p.Glu512= | synonymous_variant | 3/6 | ENST00000229554.10 | NP_001010892.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1536G>A | p.Glu512= | synonymous_variant | 3/6 | 1 | NM_001010892.3 | ENSP00000229554 | P1 | |
RSPH4A | ENST00000368581.8 | c.1536G>A | p.Glu512= | synonymous_variant | 3/5 | 1 | ENSP00000357570 | |||
RSPH4A | ENST00000368580.4 | c.922-1324G>A | intron_variant | 5 | ENSP00000357569 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000554 AC: 138AN: 248994Hom.: 3 AF XY: 0.000727 AC XY: 98AN XY: 134750
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GnomAD4 exome AF: 0.000273 AC: 398AN: 1460256Hom.: 6 Cov.: 32 AF XY: 0.000391 AC XY: 284AN XY: 726108
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
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 | Ambry Genetics | Feb 09, 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. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 24, 2022 | - - |
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