7-727160-A-T

Variant names:

• chr7-727160-A-T
• NM_017802.4:c.440A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017802.4(DNAAF5):​c.440A>T​(p.Gln147Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000877 in 1,139,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.440A>T	p.Gln147Leu	missense_variant	Exon 1 of 13	ENST00000297440.11	NP_060272.3
PRKAR1B	NM_001164760.2	c.-23+50T>A		intron_variant	Intron 1 of 10	ENST00000537384.6	NP_001158232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.440A>T	p.Gln147Leu	missense_variant	Exon 1 of 13	1	NM_017802.4	ENSP00000297440.6
PRKAR1B	ENST00000537384.6	c.-23+50T>A		intron_variant	Intron 1 of 10	5	NM_001164760.2	ENSP00000440449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.77e-7 AC: 1 AN: 1139864 Hom.: 0 Cov.: 31 AF XY: 0.00000180 AC XY: 1 AN XY: 556252

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.80	T
PrimateAI	Pathogenic	0.96	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.21
Sift	Benign	0.035	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.68	P
Vest4		0.35
MutPred		0.43		Gain of stability (P = 0.0955);
MVP		0.40
MPC		0.45
ClinPred		0.61	D
GERP RS		1.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		4.0
Varity_R		0.12
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-766797;