rs116329113

Variant names:

• chr8-132572067-A-G
• rs116329113
• NM_012472.6:c.*239T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_012472.6(DNAAF11):​c.*239T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 379,360 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0076 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (4 hom.)
• Consequence: DNAAF11 NM_012472.6 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.143
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-132572067-A-G is Benign according to our data. Variant chr8-132572067-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 911879.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00758 (1154/152326) while in subpopulation AFR AF = 0.0119 (493/41576). AF 95% confidence interval is 0.011. There are 10 homozygotes in GnomAd4. There are 542 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.*239T>C		3_prime_UTR	Exon 12 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.*239T>C		3_prime_UTR	Exon 11 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.*239T>C		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.*239T>C		3_prime_UTR	Exon 12 of 12	ENSP00000484634.1	Q86X45-1
	DNAAF11	ENST00000940686.1		c.*239T>C		splice_region	Exon 9 of 9	ENSP00000610745.1
	DNAAF11	ENST00000869719.1		c.*239T>C		3_prime_UTR	Exon 12 of 12	ENSP00000539778.1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1156 AN: 152208 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00732

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.00557 AC: 1265 AN: 227034 Hom.: 4 Cov.: 3 AF XY: 0.00551 AC XY: 638 AN XY: 115812

African (AFR) AF: 0.0125 AC: 88 AN: 7018

American (AMR) AF: 0.00415 AC: 31 AN: 7462

Ashkenazi Jewish (ASJ) AF: 0.00131 AC: 11 AN: 8422

East Asian (EAS) AF: 0.00 AC: 0 AN: 20078

South Asian (SAS) AF: 0.00226 AC: 10 AN: 4430

European-Finnish (FIN) AF: 0.000388 AC: 7 AN: 18040

Middle Eastern (MID) AF: 0.00688 AC: 8 AN: 1162

European-Non Finnish (NFE) AF: 0.00690 AC: 1003 AN: 145460

Other (OTH) AF: 0.00715 AC: 107 AN: 14962

GnomAD4 genome AF: 0.00758 AC: 1154 AN: 152326 Hom.: 10 Cov.: 32 AF XY: 0.00728 AC XY: 542 AN XY: 74488

African (AFR) AF: 0.0119 AC: 493 AN: 41576

American (AMR) AF: 0.00438 AC: 67 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00732 AC: 498 AN: 68030

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00731 Hom.: 0

Bravo AF: 0.00874

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		-0.14
Mutation Taster		=98/2	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: rs116329113; hg19: chr8-133584315;