rs758280553

chr7-741423-C-Achr7-741423-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017802.4(DNAAF5):c.982C>A(p.Leu328Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,571,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L328L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0661661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF5	NM_017802.4	c.982C>A	p.Leu328Met	missense_variant	4/13	ENST00000297440.11
DNAAF5	XM_024446813.2	c.982C>A	p.Leu328Met	missense_variant	4/12
DNAAF5	NR_075098.2	n.942C>A		non_coding_transcript_exon_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF5	ENST00000297440.11	c.982C>A	p.Leu328Met	missense_variant	4/13	1	NM_017802.4	P1
DNAAF5	ENST00000440747.5	c.388C>A	p.Leu130Met	missense_variant	4/13	2
DNAAF5	ENST00000437419.5	c.301C>A	p.Leu101Met	missense_variant	3/5	5
DNAAF5	ENST00000438961.1	n.451C>A		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152262 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419366 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 701642

Gnomad4 AFR exome AF: 0.0000303

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152262 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74394

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.080
Sift	Benign	0.71	T
Sift4G	Benign	0.34	T
Polyphen		0.53	P
Vest4		0.22
MutPred		0.16		Gain of methylation at K325 (P = 0.086);
MVP		0.21
MPC		0.35
ClinPred		0.70	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.39

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: rs758280553; hg19: chr7-781060;