rs35504640

Variant names:

• chr16-84169905-G-A
• rs35504640
• NM_178452.6:c.1077G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-84169905-G-A
• chr16-84169905-G-C

Variant summary

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

The NM_178452.6(DNAAF1):​c.1077G>A​(p.Ala359Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,614,104 control chromosomes in the GnomAD database, including 905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (125 hom., cov: 33)
  • Exomes 𝑓: 0.029 (780 hom.)
• Consequence: DNAAF1 NM_178452.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.72
• Publications: 4 publications found

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-84169905-G-A is Benign according to our data. Variant chr16-84169905-G-A is described in ClinVar as Benign. ClinVar VariationId is 226570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. 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
	DNAAF1	NM_178452.6	MANE Select	c.1077G>A	p.Ala359Ala	synonymous	Exon 8 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.369G>A	p.Ala123Ala	synonymous	Exon 4 of 8	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.1077G>A	p.Ala359Ala	synonymous	Exon 8 of 12	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.1077G>A	p.Ala359Ala	synonymous	Exon 8 of 13	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.1077G>A	p.Ala359Ala	synonymous	Exon 8 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5174 AN: 152218 Hom.: 126 Cov.: 33

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0373

GnomAD2 exomes AF: 0.0285 AC: 7173 AN: 251426 AF XY: 0.0301

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0343

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00545

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0401

GnomAD4 exome AF: 0.0286 AC: 41855 AN: 1461768 Hom.: 780 Cov.: 32 AF XY: 0.0295 AC XY: 21428 AN XY: 727178

African (AFR) AF: 0.0572 AC: 1914 AN: 33474

American (AMR) AF: 0.0201 AC: 901 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 941 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0538 AC: 4637 AN: 86250

European-Finnish (FIN) AF: 0.00623 AC: 333 AN: 53420

Middle Eastern (MID) AF: 0.0821 AC: 466 AN: 5678

European-Non Finnish (NFE) AF: 0.0276 AC: 30652 AN: 1112010

Other (OTH) AF: 0.0332 AC: 2004 AN: 60376

GnomAD4 genome AF: 0.0340 AC: 5175 AN: 152336 Hom.: 125 Cov.: 33 AF XY: 0.0333 AC XY: 2478 AN XY: 74490

African (AFR) AF: 0.0573 AC: 2380 AN: 41570

American (AMR) AF: 0.0279 AC: 427 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4830

European-Finnish (FIN) AF: 0.00442 AC: 47 AN: 10626

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1838 AN: 68032

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0267 Hom.: 42

Bravo AF: 0.0361

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.0344

EpiControl AF: 0.0331

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-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: rs35504640; hg19: chr16-84203511;