dbSNP rs998645747: DNAAF5:p.Pro128Thr (chr7-727102-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017802.4(DNAAF5):c.382C>A(p.Pro128Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. P128S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAAF5
NM_017802.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.418

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16205034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4 link	c.382C>A	p.Pro128Thr	missense_variant	Exon 1 of 13	ENST00000297440.11	NP_060272.3	Q86Y56-1B3KPE2
PRKAR1B	NM_001164760.2 link	c.-23+108G>T		intron_variant	Intron 1 of 10	ENST00000537384.6	NP_001158232.1	P31321

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11 link	c.382C>A	p.Pro128Thr	missense_variant	Exon 1 of 13	1	NM_017802.4	ENSP00000297440.6		Q86Y56-1
PRKAR1B	ENST00000537384.6 link	c.-23+108G>T		intron_variant	Intron 1 of 10	5	NM_001164760.2	ENSP00000440449.1		P31321

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

937710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

442408

African (AFR)

AF:

0.00

AC:

AN:

18130

American (AMR)

AF:

0.00

AC:

AN:

3882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8248

East Asian (EAS)

AF:

0.00

AC:

AN:

11008

South Asian (SAS)

AF:

0.00

AC:

AN:

19276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2156

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

831408

Other (OTH)

AF:

0.00

AC:

AN:

33460

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.00058

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.92

PhyloP100

0.42

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.75

REVEL

Benign

0.066

Sift

Benign

0.030

Sift4G

Benign

0.25

Polyphen

0.33

Vest4

0.079

MutPred

0.21

Gain of glycosylation at P128 (P = 0.0253);

MVP

0.081

MPC

0.20

ClinPred

0.16

GERP RS

3.0

PromoterAI

-0.067

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.3

Varity_R

0.089

gMVP

0.44

Mutation Taster

=88/12

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over