19-55161416-A-T

Variant names:

• chr19-55161416-A-T
• rs7260320
• NM_001256715.2:c.666T>A

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.666T>A​(p.Ala222Ala) variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A222A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAAF3 NM_001256715.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 10 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=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.003 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.666T>A	p.Ala222Ala	splice_region synonymous	Exon 7 of 12	NP_001243644.1
	DNAAF3	NM_001256714.1		c.870T>A	p.Ala290Ala	splice_region synonymous	Exon 7 of 12	NP_001243643.1
	DNAAF3	NM_178837.4		c.807T>A	p.Ala269Ala	splice_region synonymous	Exon 7 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.666T>A	p.Ala222Ala	splice_region synonymous	Exon 7 of 12	ENSP00000432046.3
	DNAAF3	ENST00000455045.5	TSL:1	c.504T>A	p.Ala168Ala	splice_region synonymous	Exon 7 of 12	ENSP00000394343.1
	DNAAF3	ENST00000528412.5	TSL:1	n.*454T>A		splice_region non_coding_transcript_exon	Exon 7 of 12	ENSP00000433826.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 622928 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 322250

African (AFR) AF: 0.00 AC: 0 AN: 24656

American (AMR) AF: 0.00 AC: 0 AN: 22576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14308

East Asian (EAS) AF: 0.00 AC: 0 AN: 12354

South Asian (SAS) AF: 0.00 AC: 0 AN: 59138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 426648

Other (OTH) AF: 0.00 AC: 0 AN: 27350

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 2248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.76
PhyloP100		-0.0030

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: rs7260320; hg19: chr19-55672784;