19-55162241-C-A

Variant names:

• chr19-55162241-C-A
• rs1048936417
• NM_001256715.2:c.372G>T

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.372G>T​(p.Pro124Pro) 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. P124P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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=-0.65).
• BP7: Synonymous conserved (PhyloP=1.37 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	NM_001256715.2	MANE Select	c.372G>T	p.Pro124Pro	synonymous	Exon 5 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.576G>T	p.Pro192Pro	synonymous	Exon 5 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.513G>T	p.Pro171Pro	synonymous	Exon 5 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.372G>T	p.Pro124Pro	synonymous	Exon 5 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.210G>T	p.Pro70Pro	synonymous	Exon 5 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*160G>T		non_coding_transcript_exon	Exon 5 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1097422 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 518424

African (AFR) AF: 0.00 AC: 0 AN: 23044

American (AMR) AF: 0.00 AC: 0 AN: 8890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14400

East Asian (EAS) AF: 0.00 AC: 0 AN: 26566

South Asian (SAS) AF: 0.00 AC: 0 AN: 20064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 921444

Other (OTH) AF: 0.00 AC: 0 AN: 44034

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	-0.65
CADD	Benign	7.0
DANN	Benign	0.91
PhyloP100		1.4

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: rs1048936417; hg19: chr19-55673609;