rs779796065
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001010892.3(RSPH4A):c.1928A>T(p.Asn643Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,609,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001010892.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.1928A>T | p.Asn643Ile | missense_variant | 6/6 | ENST00000229554.10 | |
LOC124901386 | XR_007059721.1 | n.459+1587T>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1928A>T | p.Asn643Ile | missense_variant | 6/6 | 1 | NM_001010892.3 | P1 | |
RSPH4A | ENST00000368581.8 | c.1792A>T | p.Ile598Phe | missense_variant | 5/5 | 1 | |||
RSPH4A | ENST00000368580.4 | c.1187A>T | p.Asn396Ile | missense_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000403 AC: 10AN: 248124Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134396
GnomAD4 exome AF: 0.0000460 AC: 67AN: 1456956Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 28AN XY: 724856
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74304
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2017 | This sequence change replaces asparagine with isoleucine at codon 643 of the RSPH4A protein (p.Asn643Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs779796065, ExAC 0.002%) but has not been reported in the literature in individuals with a RSPH4A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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