rs3848618

Variant names:

• chr19-55162286-T-C
• rs3848618
• NM_001256715.2:c.327A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-55162286-T-C
• chr19-55162286-T-A

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.327A>G​(p.Arg109Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 1,250,556 control chromosomes in the GnomAD database, including 2,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (740 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1923 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.505
• Publications: 14 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=-0.93).
• BP6: Variant 19-55162286-T-C is Benign according to our data. Variant chr19-55162286-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.505 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.327A>G	p.Arg109Arg	synonymous	Exon 5 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.531A>G	p.Arg177Arg	synonymous	Exon 5 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.468A>G	p.Arg156Arg	synonymous	Exon 5 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.327A>G	p.Arg109Arg	synonymous	Exon 5 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.165A>G	p.Arg55Arg	synonymous	Exon 5 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*115A>G		non_coding_transcript_exon	Exon 5 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9402 AN: 152104 Hom.: 729 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0721

GnomAD2 exomes AF: 0.0347 AC: 769 AN: 22156 AF XY: 0.0340

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.0314

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0633

GnomAD4 exome AF: 0.0376 AC: 41316 AN: 1098332 Hom.: 1923 Cov.: 31 AF XY: 0.0377 AC XY: 19531 AN XY: 518684

African (AFR) AF: 0.0490 AC: 1128 AN: 23036

American (AMR) AF: 0.289 AC: 2524 AN: 8740

Ashkenazi Jewish (ASJ) AF: 0.0220 AC: 316 AN: 14378

East Asian (EAS) AF: 0.247 AC: 6539 AN: 26524

South Asian (SAS) AF: 0.117 AC: 2314 AN: 19792

European-Finnish (FIN) AF: 0.0322 AC: 1172 AN: 36412

Middle Eastern (MID) AF: 0.0398 AC: 180 AN: 4518

European-Non Finnish (NFE) AF: 0.0268 AC: 24678 AN: 920960

Other (OTH) AF: 0.0561 AC: 2465 AN: 43972

GnomAD4 genome AF: 0.0620 AC: 9435 AN: 152224 Hom.: 740 Cov.: 33 AF XY: 0.0666 AC XY: 4957 AN XY: 74426

African (AFR) AF: 0.0496 AC: 2059 AN: 41528

American (AMR) AF: 0.214 AC: 3265 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1139 AN: 5166

South Asian (SAS) AF: 0.129 AC: 622 AN: 4824

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1820 AN: 68022

Other (OTH) AF: 0.0728 AC: 154 AN: 2116

Alfa AF: 0.0449 Hom.: 1702

Bravo AF: 0.0771

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

ClinVar submissions

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	-0.93
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.51
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: rs3848618; hg19: chr19-55673654; COSMIC: COSV61279389; COSMIC: COSV61279389;