19-55166587-G-T

Variant names:

• chr19-55166587-G-T
• rs772986651
• NM_001256715.2:c.-69C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256714.1(DNAAF3):​c.62C>A​(p.Pro21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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. P21R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF3 NM_001256714.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114730775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256714.1. 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.-69C>A		5_prime_UTR	Exon 1 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.62C>A	p.Pro21Gln	missense	Exon 1 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.62C>A	p.Pro21Gln	missense	Exon 1 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.-69C>A		5_prime_UTR	Exon 1 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.-318C>A		5_prime_UTR	Exon 1 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.-80C>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.1
DANN	Benign	0.79
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.031
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.29	T
Vest4		0.19
MutPred		0.43		Gain of catalytic residue at P21 (P = 0.0029)
MVP		0.040
MPC		0.45
ClinPred		0.56	D
GERP RS		-4.1
PromoterAI		-0.019	Neutral
gMVP		0.19
Mutation Taster		=100/0	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: rs772986651; hg19: chr19-55677955;