Genetic Variant NM_001256715.2:c.891G>C (chr19-55161086-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001256715.2(DNAAF3):c.891G>C(p.Thr297Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,710 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. T297T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

DNAAF3
NM_001256715.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

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 -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 19-55161086-C-G is Benign according to our data. Variant chr19-55161086-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2914479.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.549 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	UniProt
DNAAF3	NM_001256715.2	MANE Select	c.891G>C	p.Thr297Thr	synonymous	Exon 8 of 12	NP_001243644.1	Q8N9W5-1
DNAAF3	NM_001256714.1		c.1095G>C	p.Thr365Thr	synonymous	Exon 8 of 12	NP_001243643.1	Q8N9W5-3
DNAAF3	NM_178837.4		c.1032G>C	p.Thr344Thr	synonymous	Exon 8 of 12	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.891G>C	p.Thr297Thr	synonymous	Exon 8 of 12	ENSP00000432046.3	Q8N9W5-1
DNAAF3	ENST00000455045.5	TSL:1	c.729G>C	p.Thr243Thr	synonymous	Exon 8 of 12	ENSP00000394343.1	Q8N9W5-7
DNAAF3	ENST00000528412.5	TSL:1	n.*679G>C		non_coding_transcript_exon	Exon 8 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000138

AC:

AN:

144736

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000814

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

AF:

0.00000216

AC:

AN:

1390710

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31494

American (AMR)

AF:

0.0000841

AC:

AN:

35662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35708

South Asian (SAS)

AF:

0.00

AC:

AN:

79116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078368

Other (OTH)

AF:

0.00

AC:

AN:

57744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.55

PromoterAI

0.00020

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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