NM_001010892.3:c.1879A>C
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001010892.3(RSPH4A):c.1879A>C(p.Asn627His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,606,826 control chromosomes in the GnomAD database, including 6,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N627K) has been classified as Uncertain significance.
Frequency
Consequence
NM_001010892.3 missense
Scores
Clinical Significance
Conservation
Publications
- primary ciliary dyskinesia 11Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1879A>C | p.Asn627His | missense_variant | Exon 5 of 6 | 1 | NM_001010892.3 | ENSP00000229554.5 | ||
RSPH4A | ENST00000368581.8 | c.1743A>C | p.Pro581Pro | synonymous_variant | Exon 4 of 5 | 1 | ENSP00000357570.4 | |||
RSPH4A | ENST00000368580.4 | c.1138A>C | p.Asn380His | missense_variant | Exon 4 of 5 | 5 | ENSP00000357569.4 |
Frequencies
GnomAD3 genomes AF: 0.113 AC: 17162AN: 151826Hom.: 1633 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0925 AC: 23267AN: 251438 AF XY: 0.0857 show subpopulations
GnomAD4 exome AF: 0.0621 AC: 90341AN: 1454882Hom.: 4650 Cov.: 29 AF XY: 0.0623 AC XY: 45124AN XY: 724174 show subpopulations
GnomAD4 genome AF: 0.113 AC: 17202AN: 151944Hom.: 1643 Cov.: 31 AF XY: 0.112 AC XY: 8332AN XY: 74276 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:2
Asn627His in exon 5 of RSPH4A: This variant is not expected to have clinical sig nificance because it has been identified in 22.7% (999/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs9488991). -
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Primary ciliary dyskinesia Benign:2
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. -
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Primary ciliary dyskinesia 11 Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at