rs78581255
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_017802.4(DNAAF5):c.477G>A(p.Ala159Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,346,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
DNAAF5
NM_017802.4 synonymous
NM_017802.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00800
Genes affected
DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]
PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 7-727197-G-A is Benign according to our data. Variant chr7-727197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.008 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00184 (276/150010) while in subpopulation AFR AF= 0.00641 (264/41180). AF 95% confidence interval is 0.00578. There are 0 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DNAAF5 | ENST00000297440.11 | c.477G>A | p.Ala159Ala | synonymous_variant | Exon 1 of 13 | 1 | NM_017802.4 | ENSP00000297440.6 | ||
| PRKAR1B | ENST00000537384.6 | c.-23+13C>T | intron_variant | Intron 1 of 10 | 5 | NM_001164760.2 | ENSP00000440449.1 |
Frequencies
GnomAD3 genomes 0.00184 AC: 276AN: 149902Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000137 AC: 7AN: 50946Hom.: 0 AF XY: 0.000164 AC XY: 5AN XY: 30448
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GnomAD4 exome AF: 0.000140 AC: 168AN: 1196200Hom.: 0 Cov.: 31 AF XY: 0.000123 AC XY: 72AN XY: 586950
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GnomAD4 genome 0.00184 AC: 276AN: 150010Hom.: 0 Cov.: 32 AF XY: 0.00172 AC XY: 126AN XY: 73180
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Aug 24, 2018
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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. -
Jan 05, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
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PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at