dbSNP rs763786288: DNAAF3:c.664-9C>T (chr19-55161427-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001256715.2(DNAAF3):c.664-9C>T variant causes a intron 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 (★★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAAF3
NM_001256715.2 intron

Scores

Splicing: ADA: 0.00001917

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.26

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-55161427-G-A is Benign according to our data. Variant chr19-55161427-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 257693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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	Effect	Exon Rank	Protein	UniProt
DNAAF3	NM_001256715.2	MANE Select	c.664-9C>T	intron	N/A	NP_001243644.1	Q8N9W5-1
DNAAF3	NM_001256714.1		c.868-9C>T	intron	N/A	NP_001243643.1	Q8N9W5-3
DNAAF3	NM_178837.4		c.805-9C>T	intron	N/A	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.664-9C>T	intron	N/A	ENSP00000432046.3	Q8N9W5-1
DNAAF3	ENST00000455045.5	TSL:1	c.502-9C>T	intron	N/A	ENSP00000394343.1	Q8N9W5-7
DNAAF3	ENST00000528412.5	TSL:1	n.*452-9C>T	intron	N/A	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000488

AC:

AN:

184362

AF XY:

0.0000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000433

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000240

AC:

AN:

457978

Hom.:

Cov.:

AF XY:

0.0000161

AC XY:

AN XY:

247782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14906

American (AMR)

AF:

0.000394

AC:

AN:

22866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10514

East Asian (EAS)

AF:

0.00

AC:

AN:

13956

South Asian (SAS)

AF:

0.00

AC:

AN:

61254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2430

European-Non Finnish (NFE)

AF:

0.00000711

AC:

AN:

281184

Other (OTH)

AF:

0.00

AC:

AN:

19972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.652

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

(source)

DANN

Benign

0.95

PhyloP100

-1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over