7-756956-G-C

Position:

• chr7-756956-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017802.4(DNAAF5):​c.1432G>C​(p.Glu478Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. E478K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17964387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.1432G>C	p.Glu478Gln	missense_variant	6/13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.1432G>C	p.Glu478Gln	missense_variant	6/12		XP_024302581.1
DNAAF5	NR_075098.2	n.1392G>C		non_coding_transcript_exon_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1432G>C	p.Glu478Gln	missense_variant	6/13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000440747.5	c.835G>C	p.Glu279Gln	missense_variant	6/13	2		ENSP00000403165.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000408 AC: 1 AN: 245224 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454586 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723838

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.048
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.92	P
Vest4		0.28
MutPred		0.28		Loss of solvent accessibility (P = 0.3103);
MVP		0.040
MPC		0.22
ClinPred		0.098	T
GERP RS		2.4
Varity_R		0.047
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs118139460; hg19: chr7-796593;