rs146442289

Variant names:

• chr19-55160788-G-A
• rs146442289
• NM_001256715.2:c.913-13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001256715.2(DNAAF3):​c.913-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,606,570 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (15 hom.)
• Consequence: DNAAF3 NM_001256715.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0450
• 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)

ENSG00000267110 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-55160788-G-A is Benign according to our data. Variant chr19-55160788-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0026 (396/152374) while in subpopulation NFE AF = 0.00385 (262/68044). AF 95% confidence interval is 0.00347. There are 1 homozygotes in GnomAd4. There are 202 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR,AD gene

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.913-13C>T		intron	N/A	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1117-13C>T		intron	N/A	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1054-13C>T		intron	N/A	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.913-13C>T		intron	N/A	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.751-13C>T		intron	N/A	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*701-13C>T		intron	N/A	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 396 AN: 152256 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00279 AC: 665 AN: 238632 AF XY: 0.00283

Gnomad AFR exome AF: 0.000409

Gnomad AMR exome AF: 0.000893

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00722

Gnomad NFE exome AF: 0.00394

Gnomad OTH exome AF: 0.00439

GnomAD4 exome AF: 0.00402 AC: 5852 AN: 1454196 Hom.: 15 Cov.: 33 AF XY: 0.00397 AC XY: 2869 AN XY: 723564

African (AFR) AF: 0.000749 AC: 25 AN: 33388

American (AMR) AF: 0.000888 AC: 39 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.00415 AC: 108 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.000743 AC: 64 AN: 86134

European-Finnish (FIN) AF: 0.00772 AC: 375 AN: 48562

Middle Eastern (MID) AF: 0.00813 AC: 46 AN: 5656

European-Non Finnish (NFE) AF: 0.00452 AC: 5025 AN: 1110634

Other (OTH) AF: 0.00282 AC: 170 AN: 60240

GnomAD4 genome AF: 0.00260 AC: 396 AN: 152374 Hom.: 1 Cov.: 33 AF XY: 0.00271 AC XY: 202 AN XY: 74518

African (AFR) AF: 0.000745 AC: 31 AN: 41592

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00489 AC: 52 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00385 AC: 262 AN: 68044

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00369 Hom.: 0

Bravo AF: 0.00235

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.96
PhyloP100		0.045
PromoterAI		0.041	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs146442289;

hg19: chr19-55672156;