NM_001256715.2:c.485G>A

Variant names:

• chr19-55161821-C-T
• rs1060502832
• NM_001256715.2:c.485G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001256715.2(DNAAF3):​c.485G>A​(p.Arg162His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,282,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R162S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 1 publications found

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3541344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256715.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	NM_001256715.2	MANE Select	c.485G>A	p.Arg162His	missense	Exon 6 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.689G>A	p.Arg230His	missense	Exon 6 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.626G>A	p.Arg209His	missense	Exon 6 of 12	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.485G>A	p.Arg162His	missense	Exon 6 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.323G>A	p.Arg108His	missense	Exon 6 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*273G>A		non_coding_transcript_exon	Exon 6 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 54178 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000624 AC: 8 AN: 1282656 Hom.: 0 Cov.: 32 AF XY: 0.00000642 AC XY: 4 AN XY: 623062

African (AFR) AF: 0.00 AC: 0 AN: 26758

American (AMR) AF: 0.00 AC: 0 AN: 21668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18994

East Asian (EAS) AF: 0.0000311 AC: 1 AN: 32200

South Asian (SAS) AF: 0.00 AC: 0 AN: 65062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4260

European-Non Finnish (NFE) AF: 0.00000681 AC: 7 AN: 1027796

Other (OTH) AF: 0.00 AC: 0 AN: 53078

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000514 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.31		Loss of MoRF binding (P = 0.0331)
MVP		0.33
MPC		3.0
ClinPred		0.95	D
GERP RS		3.7
Varity_R		0.057
gMVP		0.57
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1060502832; hg19: chr19-55673189; COSMIC: COSV105247239; COSMIC: COSV105247239;