NM_017802.4:c.1269C>T

Variant names:

• chr7-756793-C-T
• rs73036225
• NM_017802.4:c.1269C>T

Variant summary

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

The NM_017802.4(DNAAF5):​c.1269C>T​(p.Ser423Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,080 control chromosomes in the GnomAD database, including 33,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2135 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31446 hom.)
• Consequence: DNAAF5 NM_017802.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.22
• Publications: 10 publications found

Genes affected

DNAAF5 (HGNC:26013): (dynein axonemal assembly factor 5) The protein encoded by this gene is essential for the preassembly or stability of axonemal dynein arms, and is found only in organisms with motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia-18, a disorder characterized by abnormalities of motile cilia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DNAAF5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 18

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.069).
• BP6: Variant 7-756793-C-T is Benign according to our data. Variant chr7-756793-C-T is described in ClinVar as Benign. ClinVar VariationId is 260925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	NM_017802.4	MANE Select	c.1269C>T	p.Ser423Ser	synonymous	Exon 6 of 13	NP_060272.3
	DNAAF5	NR_075098.2		n.1229C>T		non_coding_transcript_exon	Exon 6 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF5	ENST00000297440.11	TSL:1 MANE Select	c.1269C>T	p.Ser423Ser	synonymous	Exon 6 of 13	ENSP00000297440.6
	DNAAF5	ENST00000440747.5	TSL:2	c.672C>T	p.Ser224Ser	synonymous	Exon 6 of 13	ENSP00000403165.1
	DNAAF5	ENST00000437419.5	TSL:5	c.*1C>T		downstream_gene	N/A	ENSP00000410788.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21894 AN: 152152 Hom.: 2138 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.162 AC: 40769 AN: 251052 AF XY: 0.172

Gnomad AFR exome AF: 0.0371

Gnomad AMR exome AF: 0.0938

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.00152

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.200 AC: 292268 AN: 1460810 Hom.: 31446 Cov.: 34 AF XY: 0.201 AC XY: 146049 AN XY: 726718

African (AFR) AF: 0.0338 AC: 1133 AN: 33474

American (AMR) AF: 0.0997 AC: 4456 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6718 AN: 26122

East Asian (EAS) AF: 0.000907 AC: 36 AN: 39694

South Asian (SAS) AF: 0.205 AC: 17700 AN: 86246

European-Finnish (FIN) AF: 0.112 AC: 5923 AN: 53054

Middle Eastern (MID) AF: 0.236 AC: 1358 AN: 5762

European-Non Finnish (NFE) AF: 0.219 AC: 243688 AN: 1111380

Other (OTH) AF: 0.186 AC: 11256 AN: 60364

GnomAD4 genome AF: 0.144 AC: 21888 AN: 152270 Hom.: 2135 Cov.: 33 AF XY: 0.139 AC XY: 10364 AN XY: 74454

African (AFR) AF: 0.0411 AC: 1710 AN: 41572

American (AMR) AF: 0.136 AC: 2084 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.188 AC: 906 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10618

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14548 AN: 67988

Other (OTH) AF: 0.170 AC: 360 AN: 2114

Alfa AF: 0.192 Hom.: 1571

Bravo AF: 0.142

Asia WGS AF: 0.0710 AC: 247 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.224

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.28
DANN	Benign	0.49
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs73036225; hg19: chr7-796430; COSMIC: COSV108096223; COSMIC: COSV108096223;