NM_001256715.2:c.485G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001256715.2(DNAAF3):​c.485G>T​(p.Arg162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000078 in 1,282,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). 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: 7.8e-7 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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>T	p.Arg162Leu	missense	Exon 6 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.689G>T	p.Arg230Leu	missense	Exon 6 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.626G>T	p.Arg209Leu	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>T	p.Arg162Leu	missense	Exon 6 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.323G>T	p.Arg108Leu	missense	Exon 6 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*273G>T		non_coding_transcript_exon	Exon 6 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.80e-7 AC: 1 AN: 1282656 Hom.: 0 Cov.: 32 AF XY: 0.00000160 AC XY: 1 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: 0.00 AC: 0 AN: 32200

South Asian (SAS) AF: 0.0000154 AC: 1 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: 0.00 AC: 0 AN: 1027796

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.20
Sift	Benign	0.061	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.97	D
Vest4		0.60
MutPred		0.34		Loss of MoRF binding (P = 0.0402)
MVP		0.33
MPC		1.9
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.16
gMVP		0.73
Mutation Taster		=76/24	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;