19-55159098-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001256715.2(DNAAF3):​c.1590G>T​(p.Pro530Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,206 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44
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-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 19-55159098-C-A is Benign according to our data. Variant chr19-55159098-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3725217.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.44 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAAF3NM_001256715.2 linkc.1590G>T p.Pro530Pro synonymous_variant Exon 12 of 12 ENST00000524407.7 NP_001243644.1 Q8N9W5-1
DNAAF3NM_001256714.1 linkc.1791G>T p.Pro597Pro synonymous_variant Exon 12 of 12 NP_001243643.1 Q8N9W5-3
DNAAF3NM_178837.4 linkc.1731G>T p.Pro577Pro synonymous_variant Exon 12 of 12 NP_849159.2 Q8N9W5-6
DNAAF3NM_001256716.2 linkc.1428G>T p.Pro476Pro synonymous_variant Exon 12 of 12 NP_001243645.1 Q8N9W5-7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAAF3ENST00000524407.7 linkc.1590G>T p.Pro530Pro synonymous_variant Exon 12 of 12 1 NM_001256715.2 ENSP00000432046.3 Q8N9W5-1
ENSG00000267110ENST00000587871.1 linkn.478+95G>T intron_variant Intron 4 of 8 5 ENSP00000473050.1 M0R381

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456206
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
723756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Nov 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.20
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55670466; COSMIC: COSV61277436; COSMIC: COSV61277436; API