chr21-42493014-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_080860.4(RSPH1):c.120C>T(p.Asn40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,614,142 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0094 ( 30 hom., cov: 33)
Exomes 𝑓: 0.00098 ( 29 hom. )
Consequence
RSPH1
NM_080860.4 synonymous
NM_080860.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.23
Genes affected
RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 21-42493014-G-A is Benign according to our data. Variant chr21-42493014-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.23 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00937 (1427/152258) while in subpopulation AFR AF= 0.0324 (1346/41524). AF 95% confidence interval is 0.031. There are 30 homozygotes in gnomad4. There are 690 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.120C>T | p.Asn40= | synonymous_variant | 2/9 | ENST00000291536.8 | |
RSPH1 | XM_011529786.2 | c.120C>T | p.Asn40= | synonymous_variant | 2/8 | ||
RSPH1 | NM_001286506.2 | c.55-151C>T | intron_variant | ||||
RSPH1 | XM_005261208.3 | c.67+3106C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.120C>T | p.Asn40= | synonymous_variant | 2/9 | 1 | NM_080860.4 | P1 | |
RSPH1 | ENST00000398352.3 | c.55-151C>T | intron_variant | 5 | |||||
RSPH1 | ENST00000493019.1 | n.180C>T | non_coding_transcript_exon_variant | 2/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00937 AC: 1425AN: 152142Hom.: 30 Cov.: 33
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GnomAD3 exomes AF: 0.00231 AC: 581AN: 251480Hom.: 13 AF XY: 0.00174 AC XY: 237AN XY: 135916
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GnomAD4 exome AF: 0.000984 AC: 1438AN: 1461884Hom.: 29 Cov.: 31 AF XY: 0.000846 AC XY: 615AN XY: 727244
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GnomAD4 genome AF: 0.00937 AC: 1427AN: 152258Hom.: 30 Cov.: 33 AF XY: 0.00927 AC XY: 690AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2022 | See Variant Classification Assertion Criteria. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at