rs41289942
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001010892.3(RSPH4A):c.731G>A(p.Arg244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,611,804 control chromosomes in the GnomAD database, including 432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001010892.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH4A | NM_001010892.3 | c.731G>A | p.Arg244His | missense_variant | 2/6 | ENST00000229554.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.731G>A | p.Arg244His | missense_variant | 2/6 | 1 | NM_001010892.3 | P1 | |
RSPH4A | ENST00000368581.8 | c.731G>A | p.Arg244His | missense_variant | 2/5 | 1 | |||
RSPH4A | ENST00000368580.4 | c.731G>A | p.Arg244His | missense_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0162 AC: 2459AN: 152106Hom.: 34 Cov.: 33
GnomAD3 exomes AF: 0.0200 AC: 5012AN: 250896Hom.: 65 AF XY: 0.0209 AC XY: 2837AN XY: 135638
GnomAD4 exome AF: 0.0205 AC: 29901AN: 1459580Hom.: 396 Cov.: 30 AF XY: 0.0209 AC XY: 15188AN XY: 726246
GnomAD4 genome ? AF: 0.0162 AC: 2465AN: 152224Hom.: 36 Cov.: 33 AF XY: 0.0155 AC XY: 1155AN XY: 74440
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Arg244His in exon 2 of RSPH4A: This variant is not expected to have clinical sig nificance because it has been identified in 2.3% (200/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs41289942). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia 11 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 28, 2023 | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2014 | This alteration is classified as 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 | Invitae | Jan 30, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | RSPH4A: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 11, 2020 | This variant is associated with the following publications: (PMID: 31213628) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at