7-763870-G-T

Variant names:

• chr7-763870-G-T
• rs760358814
• NM_017802.4:c.1679G>T

Variant summary

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

The NM_017802.4(DNAAF5):​c.1679G>T​(p.Arg560Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: DNAAF5 NM_017802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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 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=0.20495936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF5	NM_017802.4	c.1679G>T	p.Arg560Leu	missense_variant	Exon 8 of 13	ENST00000297440.11	NP_060272.3
DNAAF5	XM_024446813.2	c.1679G>T	p.Arg560Leu	missense_variant	Exon 8 of 12		XP_024302581.1
DNAAF5	NR_075098.2	n.1639G>T		non_coding_transcript_exon_variant	Exon 8 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF5	ENST00000297440.11	c.1679G>T	p.Arg560Leu	missense_variant	Exon 8 of 13	1	NM_017802.4	ENSP00000297440.6
DNAAF5	ENST00000440747.5	c.1082G>T	p.Arg361Leu	missense_variant	Exon 8 of 13	2		ENSP00000403165.1
DNAAF5	ENST00000491496.1	n.-37G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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 Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74388

Gnomad4 AFR AF: 0.0000241

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Benign	0.040	D
Sift4G	Uncertain	0.042	D
Polyphen		0.79	P
Vest4		0.48
MutPred		0.35		Loss of methylation at K561 (P = 0.0626);
MVP		0.085
MPC		0.30
ClinPred		0.83	D
GERP RS		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.13
gMVP		0.35

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: rs760358814; hg19: chr7-803507;