rs56726774

Variant names:

• chr19-55161796-T-C
• rs56726774
• NM_001256715.2:c.510A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001256715.2(DNAAF3):​c.510A>G​(p.Val170Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,480,518 control chromosomes in the GnomAD database, including 4,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (774 hom., cov: 32)
  • Exomes 𝑓: 0.046 (4014 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.0250
• Publications: 9 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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-55161796-T-C is Benign according to our data. Variant chr19-55161796-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.025 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

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.510A>G	p.Val170Val	synonymous	Exon 6 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.714A>G	p.Val238Val	synonymous	Exon 6 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.651A>G	p.Val217Val	synonymous	Exon 6 of 12	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.510A>G	p.Val170Val	synonymous	Exon 6 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.348A>G	p.Val116Val	synonymous	Exon 6 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*298A>G		non_coding_transcript_exon	Exon 6 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9959 AN: 152184 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0750

GnomAD2 exomes AF: 0.126 AC: 11474 AN: 90960 AF XY: 0.115

Gnomad AFR exome AF: 0.0641

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.0373

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0851

GnomAD4 exome AF: 0.0459 AC: 60955 AN: 1328216 Hom.: 4014 Cov.: 33 AF XY: 0.0470 AC XY: 30499 AN XY: 649138

African (AFR) AF: 0.0625 AC: 1825 AN: 29206

American (AMR) AF: 0.332 AC: 9346 AN: 28180

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 461 AN: 21336

East Asian (EAS) AF: 0.241 AC: 8277 AN: 34334

South Asian (SAS) AF: 0.114 AC: 8052 AN: 70646

European-Finnish (FIN) AF: 0.0332 AC: 1212 AN: 36552

Middle Eastern (MID) AF: 0.0406 AC: 174 AN: 4286

European-Non Finnish (NFE) AF: 0.0271 AC: 28463 AN: 1048664

Other (OTH) AF: 0.0572 AC: 3145 AN: 55012

GnomAD4 genome AF: 0.0656 AC: 9992 AN: 152302 Hom.: 774 Cov.: 32 AF XY: 0.0701 AC XY: 5218 AN XY: 74472

African (AFR) AF: 0.0612 AC: 2545 AN: 41578

American (AMR) AF: 0.216 AC: 3301 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1139 AN: 5162

South Asian (SAS) AF: 0.129 AC: 625 AN: 4834

European-Finnish (FIN) AF: 0.0276 AC: 293 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1846 AN: 68016

Other (OTH) AF: 0.0756 AC: 160 AN: 2116

Alfa AF: 0.0412 Hom.: 57

Bravo AF: 0.0809

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	3	Primary ciliary dyskinesia (3)
-	-	2	not provided (2)
-	-	1	Dilated Cardiomyopathy, Recessive (1)
-	-	1	Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome (1)
-	-	1	Familial restrictive cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.6
DANN	Benign	0.45
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56726774; hg19: chr19-55673164; COSMIC: COSV61275414; COSMIC: COSV61275414;