rs9488991
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001010892.3(RSPH4A):āc.1879A>Cā(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 (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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
Genome browser will be placed here
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.1879A>C | p.Asn627His | missense_variant | 5/6 | ENST00000229554.10 | |
LOC124901386 | XR_007059721.1 | n.460-525T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH4A | ENST00000229554.10 | c.1879A>C | p.Asn627His | missense_variant | 5/6 | 1 | NM_001010892.3 | P1 | |
RSPH4A | ENST00000368581.8 | c.1743A>C | p.Pro581= | synonymous_variant | 4/5 | 1 | |||
RSPH4A | ENST00000368580.4 | c.1138A>C | p.Asn380His | missense_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.113 AC: 17162AN: 151826Hom.: 1633 Cov.: 31
GnomAD3 exomes AF: 0.0925 AC: 23267AN: 251438Hom.: 2007 AF XY: 0.0857 AC XY: 11640AN XY: 135888
GnomAD4 exome AF: 0.0621 AC: 90341AN: 1454882Hom.: 4650 Cov.: 29 AF XY: 0.0623 AC XY: 45124AN XY: 724174
GnomAD4 genome ? AF: 0.113 AC: 17202AN: 151944Hom.: 1643 Cov.: 31 AF XY: 0.112 AC XY: 8332AN XY: 74276
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 | 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). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 24, 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 31, 2024 | - - |
Primary ciliary dyskinesia 11 Benign:1
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 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
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at