chr6-116616860-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001010892.3(RSPH4A):āc.237A>Gā(p.Thr79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,962 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 32)
Exomes š: 0.000069 ( 0 hom. )
Consequence
RSPH4A
NM_001010892.3 synonymous
NM_001010892.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.386
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 6-116616860-A-G is Benign according to our data. Variant chr6-116616860-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355118.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.386 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| RSPH4A | NM_001010892.3 | c.237A>G | p.Thr79= | synonymous_variant | 1/6 | ENST00000229554.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RSPH4A | ENST00000229554.10 | c.237A>G | p.Thr79= | synonymous_variant | 1/6 | 1 | NM_001010892.3 | P1 | |
| RSPH4A | ENST00000368581.8 | c.237A>G | p.Thr79= | synonymous_variant | 1/5 | 1 | |||
| RSPH4A | ENST00000368580.4 | c.237A>G | p.Thr79= | synonymous_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251194Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135800
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GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727234
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GnomAD4 genome 0.0000723 AC: 11AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74276
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 11 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Primary ciliary dyskinesia Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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