rs78620801

Positions:

chr8-132572364-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012472.6(DNAAF11):c.1343T>C(p.Ile448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,042 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 22 hom. )

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.17

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=0.0027182996).

BP6

Variant 8-132572364-A-G is Benign according to our data. Variant chr8-132572364-A-G is described in ClinVar as [Benign]. Clinvar id is 260272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00149 (227/152272) while in subpopulation EAS AF= 0.0389 (201/5166). AF 95% confidence interval is 0.0345. There are 5 homozygotes in gnomad4. There are 132 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF11	NM_012472.6 linkuse as main transcript	c.1343T>C	p.Ile448Thr	missense_variant	12/12	ENST00000620350.5	NP_036604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF11	ENST00000620350.5 linkuse as main transcript	c.1343T>C	p.Ile448Thr	missense_variant	12/12	1	NM_012472.6	ENSP00000484634	P1	Q86X45-1

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

228

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0390

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00340

AC:

854

AN:

251300

Hom.:

AF XY:

0.00308

AC XY:

418

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0453

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000989

AC:

1446

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

703

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0329

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00149

AC:

227

AN:

152272

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0389

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00331

AC:

402

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2019

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0050

DANN

Benign

0.30

DEOGEN2

Benign

0.0027

.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.58

T;T;.;T

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.95

.;.;N;N

REVEL

Benign

0.0030

Sift

Benign

0.57

.;.;T;T

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.043

MVP

0.055

ClinPred

0.00030

GERP RS

-2.5

Varity_R

0.020

gMVP

0.088

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