rs769656987
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_017802.4(DNAAF5):c.456C>A(p.Ala152Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 1,334,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A152A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000025 ( 0 hom. )
Consequence
DNAAF5
NM_017802.4 synonymous
NM_017802.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.60
Publications
1 publications found
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]
PRKAR1B Gene-Disease associations (from GenCC):
- Marbach-Schaaf neurodevelopmental syndromeInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- PRKAR1B-related neurodegenerative dementia with intermediate filamentsInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP7
Synonymous conserved (PhyloP=-1.6 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DNAAF5 | ENST00000297440.11 | c.456C>A | p.Ala152Ala | synonymous_variant | Exon 1 of 13 | 1 | NM_017802.4 | ENSP00000297440.6 | ||
| PRKAR1B | ENST00000537384.6 | c.-23+34G>T | intron_variant | Intron 1 of 10 | 5 | NM_001164760.2 | ENSP00000440449.1 |
Frequencies
GnomAD3 genomes 0.00000669 AC: 1AN: 149554Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
149554
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000253 AC: 3AN: 1185320Hom.: 0 Cov.: 31 AF XY: 0.00000344 AC XY: 2AN XY: 581490 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1185320
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
581490
show subpopulations
African (AFR)
AF:
AC:
0
AN:
23614
American (AMR)
AF:
AC:
0
AN:
17462
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18232
East Asian (EAS)
AF:
AC:
0
AN:
23752
South Asian (SAS)
AF:
AC:
0
AN:
54346
European-Finnish (FIN)
AF:
AC:
0
AN:
26846
Middle Eastern (MID)
AF:
AC:
0
AN:
3226
European-Non Finnish (NFE)
AF:
AC:
3
AN:
971352
Other (OTH)
AF:
AC:
0
AN:
46490
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000669 AC: 1AN: 149554Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72908 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
149554
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
72908
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41122
American (AMR)
AF:
AC:
0
AN:
15060
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3412
East Asian (EAS)
AF:
AC:
0
AN:
5126
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
9846
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66886
Other (OTH)
AF:
AC:
0
AN:
2050
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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