Genetic Variant DNAAF11:p.Pro420Thr (chr8-132572449-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_012472.6(DNAAF11):c.1258C>A(p.Pro420Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 19
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen

DNAAF11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39459044).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAAF11	NM_012472.6	MANE Select	c.1258C>A	p.Pro420Thr	missense	Exon 12 of 12	NP_036604.2
DNAAF11	NM_001321961.2		c.1198C>A	p.Pro400Thr	missense	Exon 11 of 11	NP_001308890.1
DNAAF11	NM_001321962.2		c.1012C>A	p.Pro338Thr	missense	Exon 10 of 10	NP_001308891.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.1258C>A	p.Pro420Thr	missense	Exon 12 of 12	ENSP00000484634.1	Q86X45-1
DNAAF11	ENST00000519595.5	TSL:1	c.1258C>A	p.Pro420Thr	missense	Exon 12 of 12	ENSP00000429791.1	Q86X45-1
DNAAF11	ENST00000250173.5	TSL:1	c.*122C>A		3_prime_UTR	Exon 13 of 13	ENSP00000250173.2	G5EA20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723000

African (AFR)

AF:

0.00

AC:

AN:

33088

American (AMR)

AF:

0.00

AC:

AN:

43760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25830

East Asian (EAS)

AF:

0.00

AC:

AN:

39316

South Asian (SAS)

AF:

0.00

AC:

AN:

84640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107948

Other (OTH)

AF:

0.00

AC:

AN:

60000

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.042

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.8

PhyloP100

6.3

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.43

MutPred

0.24

Loss of helix (P = 0.0376)

MVP

0.55

ClinPred

0.99

GERP RS

5.5

Varity_R

0.41

gMVP

0.43

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over