rs549691657

Variant names:

• chr8-132572127-T-C
• rs549691657
• NM_012472.6:c.*179A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_012472.6(DNAAF11):​c.*179A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 478,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: DNAAF11 NM_012472.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.762
• Publications: 0 publications found

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

DNAAF11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00129 (196/152358) while in subpopulation NFE AF = 0.0024 (163/68036). AF 95% confidence interval is 0.00209. There are 0 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012472.6. 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
	DNAAF11	NM_012472.6	MANE Select	c.*179A>G		3_prime_UTR	Exon 12 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.*179A>G		3_prime_UTR	Exon 11 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.*179A>G		3_prime_UTR	Exon 10 of 10	NP_001308891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.*179A>G		3_prime_UTR	Exon 12 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000519595.5	TSL:1	c.*179A>G		3_prime_UTR	Exon 12 of 12	ENSP00000429791.1	Q86X45-1
	DNAAF11	ENST00000869719.1		c.*179A>G		3_prime_UTR	Exon 12 of 12	ENSP00000539778.1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.00153 AC: 499 AN: 326112 Hom.: 0 Cov.: 5 AF XY: 0.00142 AC XY: 237 AN XY: 167106

African (AFR) AF: 0.000431 AC: 4 AN: 9286

American (AMR) AF: 0.000580 AC: 6 AN: 10352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10664

East Asian (EAS) AF: 0.00 AC: 0 AN: 26068

South Asian (SAS) AF: 0.00 AC: 0 AN: 12710

European-Finnish (FIN) AF: 0.000144 AC: 5 AN: 34774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1598

European-Non Finnish (NFE) AF: 0.00228 AC: 458 AN: 200846

Other (OTH) AF: 0.00131 AC: 26 AN: 19814

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152358 Hom.: 0 Cov.: 32 AF XY: 0.00115 AC XY: 86 AN XY: 74510

African (AFR) AF: 0.000409 AC: 17 AN: 41590

American (AMR) AF: 0.000784 AC: 12 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 68036

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00132

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.47
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism

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: rs549691657; hg19: chr8-133584375;