6-116616669-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001010892.3(RSPH4A):āc.46G>Cā(p.Glu16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001010892.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.46G>C | p.Glu16Gln | missense_variant | 1/6 | ENST00000229554.10 | NP_001010892.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.46G>C | p.Glu16Gln | missense_variant | 1/6 | 1 | NM_001010892.3 | ENSP00000229554 | P1 | |
RSPH4A | ENST00000368581.8 | c.46G>C | p.Glu16Gln | missense_variant | 1/5 | 1 | ENSP00000357570 | |||
RSPH4A | ENST00000368580.4 | c.46G>C | p.Glu16Gln | missense_variant | 1/5 | 5 | ENSP00000357569 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251080Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135754
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727224
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2015 | The p.E16Q variant (also known as c.46G>C), located in coding exon 1 of the RSPH4A gene, results from a G to C substitution at nucleotide position 46. The glutamic acid at codon 16 is replaced by glutamine, an amino acid with some highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 05, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 16 of the RSPH4A protein (p.Glu16Gln). This variant is present in population databases (rs780975506, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RSPH4A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at