chr16-84145357-C-CT

Position:

• chr16-84145357-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178452.6(DNAAF1):​c.-83dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,541,052 control chromosomes in the GnomAD database, including 1,079 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (336 hom., cov: 31)
  • Exomes 𝑓: 0.027 (743 hom.)
• Consequence: DNAAF1 NM_178452.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-84145357-C-CT is Benign according to our data. Variant chr16-84145357-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 320764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAAF1	NM_178452.6	c.-83dup		5_prime_UTR_variant	1/12	ENST00000378553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAAF1	ENST00000378553.10	c.-83dup		5_prime_UTR_variant	1/12	1	NM_178452.6	P1
DNAAF1	ENST00000567918.5	c.-83dup		5_prime_UTR_variant, NMD_transcript_variant	1/7	1
DNAAF1	ENST00000570298.5	n.72dup		non_coding_transcript_exon_variant	1/11	2
DNAAF1	ENST00000563093.5	c.-83dup		5_prime_UTR_variant, NMD_transcript_variant	1/11	2

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7326 AN: 151906 Hom.: 334 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0317

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0271 AC: 37623 AN: 1389028 Hom.: 743 Cov.: 30 AF XY: 0.0276 AC XY: 18897 AN XY: 685564

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.000167

Gnomad4 SAS exome AF: 0.0473

Gnomad4 FIN exome AF: 0.00600

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0329

GnomAD4 genome AF: 0.0483 AC: 7344 AN: 152024 Hom.: 336 Cov.: 31 AF XY: 0.0468 AC XY: 3479 AN XY: 74318

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0353 Hom.: 32

Bravo AF: 0.0524

Asia WGS AF: 0.0270 AC: 92 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs149813685; hg19: chr16-84178962;