19-55162211-G-C

Variant names:

• chr19-55162211-G-C
• rs1056296743
• NM_001256715.2:c.402C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001256715.2(DNAAF3):​c.402C>G​(p.Ala134Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A134A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.578 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	NM_001256715.2	MANE Select	c.402C>G	p.Ala134Ala	synonymous	Exon 5 of 12	NP_001243644.1
	DNAAF3	NM_001256714.1		c.606C>G	p.Ala202Ala	synonymous	Exon 5 of 12	NP_001243643.1
	DNAAF3	NM_178837.4		c.543C>G	p.Ala181Ala	synonymous	Exon 5 of 12	NP_849159.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.402C>G	p.Ala134Ala	synonymous	Exon 5 of 12	ENSP00000432046.3
	DNAAF3	ENST00000455045.5	TSL:1	c.240C>G	p.Ala80Ala	synonymous	Exon 5 of 12	ENSP00000394343.1
	DNAAF3	ENST00000528412.5	TSL:1	n.*190C>G		non_coding_transcript_exon	Exon 5 of 12	ENSP00000433826.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.58

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: rs1056296743; hg19: chr19-55673579;