Genetic Variant DNAAF3:p.Leu121Leu (chr19-55162250-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001256715.2(DNAAF3):c.363G>T(p.Leu121Leu) 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. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0500

Publications

0 publications found

Variant links:

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 links:

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

DNAAF3-AS1 links:

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ACMG classification

Classification was made for transcript

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=-0.36).

BP6

Variant 19-55162250-C-A is Benign according to our data. Variant chr19-55162250-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 798987.Status of the report is criteria_provided_single_submitter, 1 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF3	NM_001256715.2	MANE Select	c.363G>T	p.Leu121Leu	synonymous	Exon 5 of 12	NP_001243644.1
DNAAF3	NM_001256714.1		c.567G>T	p.Leu189Leu	synonymous	Exon 5 of 12	NP_001243643.1
DNAAF3	NM_178837.4		c.504G>T	p.Leu168Leu	synonymous	Exon 5 of 12	NP_849159.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1097118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

518204

African (AFR)

AF:

0.00

AC:

AN:

23024

American (AMR)

AF:

0.00

AC:

AN:

8920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14398

East Asian (EAS)

AF:

0.00

AC:

AN:

26528

South Asian (SAS)

AF:

0.00

AC:

AN:

19958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

921492

Other (OTH)

AF:

0.00

AC:

AN:

43984

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.7

(source)

DANN

Benign

0.90

PhyloP100

0.050

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over