19-55160006-C-T

Variant names:

• chr19-55160006-C-T
• rs891187
• NM_001256715.2:c.1056G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001256715.2(DNAAF3):​c.1056G>A​(p.Pro352Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,302,950 control chromosomes in the GnomAD database, including 38,891 homozygotes. 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. P352P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.30 (9058 hom., cov: 30)
  • Exomes 𝑓: 0.23 (29833 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -2.22
• Publications: 34 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]

ENSG00000267110 (HGNC:):

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.132).
• BP6: Variant 19-55160006-C-T is Benign according to our data. Variant chr19-55160006-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 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.1056G>A	p.Pro352Pro	synonymous	Exon 10 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1257G>A	p.Pro419Pro	synonymous	Exon 10 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1197G>A	p.Pro399Pro	synonymous	Exon 10 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.1056G>A	p.Pro352Pro	synonymous	Exon 10 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.894G>A	p.Pro298Pro	synonymous	Exon 10 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*844G>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 44409 AN: 147808 Hom.: 9032 Cov.: 30

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.214 AC: 53257 AN: 248376 AF XY: 0.216

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.234 AC: 270117 AN: 1155012 Hom.: 29833 Cov.: 31 AF XY: 0.235 AC XY: 136480 AN XY: 581438

African (AFR) AF: 0.628 AC: 19401 AN: 30890

American (AMR) AF: 0.144 AC: 5889 AN: 40894

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4569 AN: 20706

East Asian (EAS) AF: 0.238 AC: 7025 AN: 29540

South Asian (SAS) AF: 0.290 AC: 23754 AN: 81998

European-Finnish (FIN) AF: 0.247 AC: 10536 AN: 42644

Middle Eastern (MID) AF: 0.323 AC: 1498 AN: 4636

European-Non Finnish (NFE) AF: 0.216 AC: 184591 AN: 856338

Other (OTH) AF: 0.271 AC: 12854 AN: 47366

GnomAD4 genome AF: 0.301 AC: 44481 AN: 147938 Hom.: 9058 Cov.: 30 AF XY: 0.298 AC XY: 21467 AN XY: 72102

African (AFR) AF: 0.589 AC: 23890 AN: 40552

American (AMR) AF: 0.192 AC: 2836 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 620 AN: 3430

East Asian (EAS) AF: 0.233 AC: 1100 AN: 4728

South Asian (SAS) AF: 0.307 AC: 1369 AN: 4464

European-Finnish (FIN) AF: 0.211 AC: 2053 AN: 9746

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11796 AN: 66964

Other (OTH) AF: 0.290 AC: 602 AN: 2076

Alfa AF: 0.234 Hom.: 11895

Bravo AF: 0.308

Asia WGS AF: 0.313 AC: 1084 AN: 3476

EpiCase AF: 0.184

EpiControl AF: 0.183

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)
-	-	2	Primary ciliary dyskinesia 2 (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	-0.75
CADD	Benign	0.93
DANN	Benign	0.92
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs891187; hg19: chr19-55671374; COSMIC: COSV61275040; COSMIC: COSV61275040;