rs17858684

Variant names:

• chr16-84170333-C-T
• rs11644164
• NM_178452.6:c.1505C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-84170333-C-T
• chr16-84170333-C-G

Variant summary

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

The NM_178452.6(DNAAF1):​c.1505C>T​(p.Pro502Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,613,566 control chromosomes in the GnomAD database, including 107,765 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P502P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.31 (7769 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99996 hom.)
• Consequence: DNAAF1 NM_178452.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.826
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3488226E-4).
• BP6: Variant 16-84170333-C-T is Benign according to our data. Variant chr16-84170333-C-T is described in ClinVar as Benign. ClinVar VariationId is 226575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 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.1505C>T	p.Pro502Leu	missense	Exon 8 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.797C>T	p.Pro266Leu	missense	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.1505C>T	p.Pro502Leu	missense	Exon 8 of 12	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.1505C>T	p.Pro502Leu	missense	Exon 8 of 13	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.1505C>T	p.Pro502Leu	missense	Exon 8 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46589 AN: 151974 Hom.: 7761 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.318

GnomAD2 exomes AF: 0.344 AC: 85585 AN: 248686 AF XY: 0.345

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.340

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.367 AC: 535884 AN: 1461474 Hom.: 99996 Cov.: 83 AF XY: 0.364 AC XY: 264345 AN XY: 727026

African (AFR) AF: 0.151 AC: 5045 AN: 33480

American (AMR) AF: 0.383 AC: 17125 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9394 AN: 26136

East Asian (EAS) AF: 0.331 AC: 13151 AN: 39696

South Asian (SAS) AF: 0.286 AC: 24635 AN: 86248

European-Finnish (FIN) AF: 0.339 AC: 18018 AN: 53138

Middle Eastern (MID) AF: 0.333 AC: 1922 AN: 5768

European-Non Finnish (NFE) AF: 0.383 AC: 425583 AN: 1111930

Other (OTH) AF: 0.348 AC: 21011 AN: 60386

GnomAD4 genome AF: 0.306 AC: 46609 AN: 152092 Hom.: 7769 Cov.: 32 AF XY: 0.306 AC XY: 22780 AN XY: 74340

African (AFR) AF: 0.160 AC: 6628 AN: 41518

American (AMR) AF: 0.366 AC: 5593 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1261 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1704 AN: 5166

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3593 AN: 10592

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.372 AC: 25272 AN: 67956

Other (OTH) AF: 0.315 AC: 663 AN: 2106

Alfa AF: 0.358 Hom.: 21849

Bravo AF: 0.306

TwinsUK AF: 0.390 AC: 1445

ALSPAC AF: 0.383 AC: 1477

ESP6500AA AF: 0.160 AC: 700

ESP6500EA AF: 0.370 AC: 3176

ExAC AF: 0.338 AC: 40957

Asia WGS AF: 0.269 AC: 933 AN: 3478

EpiCase AF: 0.368

EpiControl AF: 0.374

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	2	Primary ciliary dyskinesia 13 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.29
DANN	Benign	0.23
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.00083	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-0.83
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.0060
Sift	Benign	0.53	T
Sift4G	Benign	0.40	T
Polyphen		0.0030	B
Vest4		0.049
MPC		0.020
ClinPred		0.00055	T
GERP RS		-0.20
Varity_R		0.019
gMVP		0.076
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: rs11644164; hg19: chr16-84203939; COSMIC: COSV57577083; COSMIC: COSV57577083;