19-55162250-C-T

Variant names:

• chr19-55162250-C-T
• rs551100219
• NM_001256715.2:c.363G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001256715.2(DNAAF3):​c.363G>A​(p.Leu121Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,249,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L121L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0500
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-55162250-C-T is Benign according to our data. Variant chr19-55162250-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 790959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.05 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.363G>A	p.Leu121Leu	synonymous	Exon 5 of 12	NP_001243644.1
	DNAAF3	NM_001256714.1		c.567G>A	p.Leu189Leu	synonymous	Exon 5 of 12	NP_001243643.1
	DNAAF3	NM_178837.4		c.504G>A	p.Leu168Leu	synonymous	Exon 5 of 12	NP_849159.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.363G>A	p.Leu121Leu	synonymous	Exon 5 of 12	ENSP00000432046.3
	DNAAF3	ENST00000455045.5	TSL:1	c.201G>A	p.Leu67Leu	synonymous	Exon 5 of 12	ENSP00000394343.1
	DNAAF3	ENST00000528412.5	TSL:1	n.*151G>A		non_coding_transcript_exon	Exon 5 of 12	ENSP00000433826.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1097118 Hom.: 0 Cov.: 31 AF XY: 0.0000154 AC XY: 8 AN XY: 518204

African (AFR) AF: 0.000130 AC: 3 AN: 23024

American (AMR) AF: 0.00 AC: 0 AN: 8920

Ashkenazi Jewish (ASJ) AF: 0.0000695 AC: 1 AN: 14398

East Asian (EAS) AF: 0.00 AC: 0 AN: 26528

South Asian (SAS) AF: 0.00 AC: 0 AN: 19958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34534

Middle Eastern (MID) AF: 0.000234 AC: 1 AN: 4280

European-Non Finnish (NFE) AF: 0.0000174 AC: 16 AN: 921492

Other (OTH) AF: 0.0000455 AC: 2 AN: 43984

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74474

African (AFR) AF: 0.0000962 AC: 4 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.6
DANN	Benign	0.93
PhyloP100		0.050
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: rs551100219; hg19: chr19-55673618;