19-55160687-A-G

Variant names:

• chr19-55160687-A-G
• rs890871
• NM_001256715.2:c.1001T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256715.2(DNAAF3):​c.1001T>C​(p.Leu334Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,613,638 control chromosomes in the GnomAD database, including 6,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (716 hom., cov: 32)
  • Exomes 𝑓: 0.048 (5484 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.170
• Publications: 17 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 (MetaRNN=0.004614681).
• BP6: Variant 19-55160687-A-G is Benign according to our data. Variant chr19-55160687-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.1001T>C	p.Leu334Pro	missense	Exon 9 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1205T>C	p.Leu402Pro	missense	Exon 9 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1142T>C	p.Leu381Pro	missense	Exon 9 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.1001T>C	p.Leu334Pro	missense	Exon 9 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.839T>C	p.Leu280Pro	missense	Exon 9 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*789T>C		non_coding_transcript_exon	Exon 9 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9217 AN: 152094 Hom.: 706 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0680

GnomAD2 exomes AF: 0.0979 AC: 24271 AN: 248004 AF XY: 0.0855

Gnomad AFR exome AF: 0.0506

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.0194

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.0290

Gnomad NFE exome AF: 0.0265

Gnomad OTH exome AF: 0.0740

GnomAD4 exome AF: 0.0478 AC: 69810 AN: 1461426 Hom.: 5484 Cov.: 33 AF XY: 0.0472 AC XY: 34326 AN XY: 727052

African (AFR) AF: 0.0496 AC: 1662 AN: 33478

American (AMR) AF: 0.357 AC: 15958 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 560 AN: 26124

East Asian (EAS) AF: 0.242 AC: 9612 AN: 39686

South Asian (SAS) AF: 0.0832 AC: 7178 AN: 86252

European-Finnish (FIN) AF: 0.0319 AC: 1692 AN: 53082

Middle Eastern (MID) AF: 0.0366 AC: 211 AN: 5764

European-Non Finnish (NFE) AF: 0.0267 AC: 29661 AN: 1111944

Other (OTH) AF: 0.0542 AC: 3276 AN: 60388

GnomAD4 genome AF: 0.0608 AC: 9249 AN: 152212 Hom.: 716 Cov.: 32 AF XY: 0.0645 AC XY: 4799 AN XY: 74428

African (AFR) AF: 0.0504 AC: 2095 AN: 41558

American (AMR) AF: 0.214 AC: 3264 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3466

East Asian (EAS) AF: 0.221 AC: 1134 AN: 5130

South Asian (SAS) AF: 0.0884 AC: 427 AN: 4832

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0266 AC: 1810 AN: 68012

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0450 Hom.: 1183

Bravo AF: 0.0772

TwinsUK AF: 0.0299 AC: 111

ALSPAC AF: 0.0288 AC: 111

ESP6500AA AF: 0.0394 AC: 152

ESP6500EA AF: 0.0213 AC: 176

ExAC AF: 0.0859 AC: 10383

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Primary ciliary dyskinesia (3)
-	-	2	not provided (2)
-	-	2	not specified (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
AlphaMissense	Benign	0.039
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.8
DANN	Benign	0.71
DEOGEN2	Benign	0.00055	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.17
PrimateAI	Benign	0.43	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.28
Sift	Benign	0.34	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.36
ClinPred		0.0080	T
GERP RS		1.5
PromoterAI		0.072	Neutral
Varity_R		0.066
gMVP		0.55
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: rs890871; hg19: chr19-55672055; COSMIC: COSV61277470; COSMIC: COSV61277470;