21-42477381-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_080860.4(RSPH1):c.637C>A(p.Gln213Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00088 in 1,612,602 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_080860.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.637C>A | p.Gln213Lys | missense_variant | 7/9 | ENST00000291536.8 | NP_543136.1 | |
RSPH1 | NM_001286506.2 | c.523C>A | p.Gln175Lys | missense_variant | 6/8 | NP_001273435.1 | ||
RSPH1 | XM_011529786.2 | c.565C>A | p.Gln189Lys | missense_variant | 6/8 | XP_011528088.1 | ||
RSPH1 | XM_005261208.3 | c.430C>A | p.Gln144Lys | missense_variant | 5/7 | XP_005261265.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.637C>A | p.Gln213Lys | missense_variant | 7/9 | 1 | NM_080860.4 | ENSP00000291536.3 | ||
RSPH1 | ENST00000398352.3 | c.523C>A | p.Gln175Lys | missense_variant | 6/8 | 5 | ENSP00000381395.3 | |||
RSPH1 | ENST00000493019.1 | n.2255C>A | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000790 AC: 119AN: 150728Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000939 AC: 236AN: 251414Hom.: 2 AF XY: 0.00105 AC XY: 143AN XY: 135910
GnomAD4 exome AF: 0.000889 AC: 1300AN: 1461756Hom.: 7 Cov.: 34 AF XY: 0.000923 AC XY: 671AN XY: 727180
GnomAD4 genome AF: 0.000789 AC: 119AN: 150846Hom.: 0 Cov.: 34 AF XY: 0.000991 AC XY: 73AN XY: 73680
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 27, 2022 | This alteration is classified as likely 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. - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | - - |
RSPH1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 28, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at