Variant chr8-132572413-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012472.6(DNAAF11):c.1294G>T(p.Val432Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,406 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DNAAF11
NM_012472.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3250298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF11	NM_012472.6 link	c.1294G>T	p.Val432Phe	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.1294G>T	p.Val432Phe	missense_variant	12/12	1	NM_012472.6	ENSP00000484634.1		Q86X45-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251058

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461406

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 19

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 14, 2018

This sequence change replaces valine with phenylalanine at codon 432 of the LRRC6 protein (p.Val432Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LRRC6-related disease. This variant is present in population databases (rs770349365, ExAC 0.001%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

D;D;.;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.7

.;M;M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

.;.;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.010

.;.;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.95

.;P;P;.

Vest4

0.34

MVP

0.58

ClinPred

0.97

GERP RS

5.5

Varity_R

0.32

gMVP

0.56

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