NM_017802.4:c.28G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_017802.4(DNAAF5):c.28G>A(p.Val10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,245,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V10L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

0 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04114619).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000328 (5/152244) while in subpopulation EAS AF = 0.000968 (5/5164). AF 95% confidence interval is 0.000381. There are 0 homozygotes in GnomAd4. There are 1 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.28G>A	p.Val10Met	missense	Exon 1 of 13	NP_060272.3
PRKAR1B	NM_001164760.2	MANE Select	c.-23+462C>T		intron	N/A	NP_001158232.1	P31321
PRKAR1B	NM_001164758.2		c.-23+842C>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.28G>A	p.Val10Met	missense	Exon 1 of 13	ENSP00000297440.6	Q86Y56-1
PRKAR1B	ENST00000537384.6	TSL:5 MANE Select	c.-23+462C>T		intron	N/A	ENSP00000440449.1	P31321
PRKAR1B	ENST00000403562.5	TSL:1	c.-23+842C>T		intron	N/A	ENSP00000385349.1	P31321

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1093752

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

518936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22948

American (AMR)

AF:

0.00

AC:

AN:

8420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14512

East Asian (EAS)

AF:

0.000790

AC:

AN:

26598

South Asian (SAS)

AF:

0.00

AC:

AN:

23790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3068

European-Non Finnish (NFE)

AF:

0.00000323

AC:

AN:

928430

Other (OTH)

AF:

0.00

AC:

AN:

44102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000328

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000968

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.2

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.022

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.46

M_CAP

Benign

0.019

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

PhyloP100

0.15

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.25

REVEL

Benign

0.011

Sift

Benign

0.17

Sift4G

Benign

0.083

Polyphen

0.44

Vest4

0.11

MutPred

0.27

Gain of helix (P = 0.2294)

MVP

0.014

MPC

0.16

ClinPred

0.16

GERP RS

0.74

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.039

gMVP

0.39

Mutation Taster

=95/5

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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