8-132572310-A-G

Position:

chr8-132572310-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012472.6(DNAAF11):c.1397T>C(p.Ile466Thr) variant causes a missense change. The variant allele was found at a frequency of 0.1 in 1,611,468 control chromosomes in the GnomAD database, including 10,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2573 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7997 hom. )

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.93

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019569993).

BP6

Variant 8-132572310-A-G is Benign according to our data. Variant chr8-132572310-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 260274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-132572310-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF11	NM_012472.6 link	c.1397T>C	p.Ile466Thr	missense_variant	12/12	ENST00000620350.5	NP_036604.2	Q86X45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5 link	c.1397T>C	p.Ile466Thr	missense_variant	12/12	1	NM_012472.6	ENSP00000484634.1		Q86X45-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22926

AN:

152032

Hom.:

2568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.0397

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0558

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0924

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.0991

AC:

24690

AN:

249022

Hom.:

1789

AF XY:

0.0986

AC XY:

13275

AN XY:

134602

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0459

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0952

AC:

138902

AN:

1459320

Hom.:

7997

Cov.:

AF XY:

0.0958

AC XY:

69526

AN XY:

725958

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.0306

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.0910

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.151

AC:

22943

AN:

152148

Hom.:

2573

Cov.:

AF XY:

0.147

AC XY:

10924

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.0876

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.0396

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.0558

Gnomad4 NFE

AF:

0.0924

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.103

Hom.:

2527

Bravo

AF:

0.160

TwinsUK

AF:

0.0898

AC:

333

ALSPAC

AF:

0.0947

AC:

365

ESP6500AA

AF:

0.294

AC:

1297

ESP6500EA

AF:

0.0967

AC:

832

ExAC

AF:

0.105

AC:

12803

Asia WGS

AF:

0.0850

AC:

301

AN:

3476

EpiCase

AF:

0.0928

EpiControl

AF:

0.0995

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 19

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Primary ciliary dyskinesia

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 08, 2016	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

.;T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D;.;D

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

.;M;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.4

.;.;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0030

.;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

0.97

.;D;D;.

Vest4

0.14

ClinPred

0.027

GERP RS

5.7

Varity_R

0.15

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over