NM_178452.6:c.1848G>A

Variant names:

• chr16-84176082-G-A
• rs76108116
• NM_178452.6:c.1848G>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_178452.6(DNAAF1):​c.1848G>A​(p.Ala616Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00918 in 1,613,946 control chromosomes in the GnomAD database, including 1,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (594 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (583 hom.)
• Consequence: DNAAF1 NM_178452.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.548
• Publications: 2 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=-0.83).
• BP6: Variant 16-84176082-G-A is Benign according to our data. Variant chr16-84176082-G-A is described in ClinVar as Benign. ClinVar VariationId is 226576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.548 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.1848G>A	p.Ala616Ala	synonymous	Exon 11 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.1140G>A	p.Ala380Ala	synonymous	Exon 7 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.1848G>A	p.Ala616Ala	synonymous	Exon 11 of 12	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.1854G>A	p.Ala618Ala	synonymous	Exon 11 of 13	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.1848G>A	p.Ala616Ala	synonymous	Exon 11 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7465 AN: 152020 Hom.: 593 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0349

GnomAD2 exomes AF: 0.0129 AC: 3225 AN: 250906 AF XY: 0.00926

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.00822

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000818

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.00668

GnomAD4 exome AF: 0.00502 AC: 7339 AN: 1461808 Hom.: 583 Cov.: 56 AF XY: 0.00434 AC XY: 3153 AN XY: 727196

African (AFR) AF: 0.174 AC: 5837 AN: 33472

American (AMR) AF: 0.00959 AC: 429 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39698

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.000247 AC: 275 AN: 1111972

Other (OTH) AF: 0.0115 AC: 695 AN: 60390

GnomAD4 genome AF: 0.0492 AC: 7483 AN: 152138 Hom.: 594 Cov.: 32 AF XY: 0.0466 AC XY: 3464 AN XY: 74366

African (AFR) AF: 0.171 AC: 7074 AN: 41464

American (AMR) AF: 0.0188 AC: 287 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 67992

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0284 Hom.: 211

Bravo AF: 0.0558

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

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	-0.83
CADD	Benign	4.6
DANN	Benign	0.52
PhyloP100		0.55
PromoterAI		0.030	Neutral
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: rs76108116; hg19: chr16-84209688;