dbSNP rs78581255: DNAAF5:p.Ala159Ala (chr7-727197-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00800

Publications

1 publications found

Variant links:

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]

DNAAF5 links:

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 syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
PRKAR1B-related neurodegenerative dementia with intermediate filaments
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRKAR1B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_017802.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF5	NM_017802.4	MANE Select	c.477G>A	p.Ala159Ala	synonymous	Exon 1 of 13	NP_060272.3
PRKAR1B	NM_001164760.2	MANE Select	c.-23+13C>T		intron	N/A	NP_001158232.1	P31321
PRKAR1B	NM_001164758.2		c.-23+393C>T		intron	N/A	NP_001158230.1	P31321

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.477G>A	p.Ala159Ala	synonymous	Exon 1 of 13	ENSP00000297440.6	Q86Y56-1
PRKAR1B	ENST00000537384.6	TSL:5 MANE Select	c.-23+13C>T		intron	N/A	ENSP00000440449.1	P31321
PRKAR1B	ENST00000403562.5	TSL:1	c.-23+393C>T		intron	N/A	ENSP00000385349.1	P31321

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

276

AN:

149902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.000486

GnomAD2 exomes

AF:

0.000137

AC:

AN:

50946

AF XY:

0.000164

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000140

AC:

168

AN:

1196200

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

586950

show subpopulations

African (AFR)

AF:

0.00619

AC:

148

AN:

23922

American (AMR)

AF:

0.000229

AC:

AN:

17472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18708

East Asian (EAS)

AF:

0.00

AC:

AN:

24554

South Asian (SAS)

AF:

0.00

AC:

AN:

54854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3278

European-Non Finnish (NFE)

AF:

0.00000204

AC:

AN:

978486

Other (OTH)

AF:

0.000296

AC:

AN:

47326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00184

AC:

276

AN:

150010

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

126

AN XY:

73180

show subpopulations

African (AFR)

AF:

0.00641

AC:

264

AN:

41180

American (AMR)

AF:

0.000661

AC:

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67032

Other (OTH)

AF:

0.000481

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00224

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.2

(source)

DANN

Benign

0.91

PhyloP100

0.0080

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over