rs538389058

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178452.6(DNAAF1):​c.1033G>A​(p.Glu345Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E345Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

DNAAF1
NM_178452.6 missense, splice_region

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.992
Variant links:
Genes affected
DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09812981).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAAF1NM_178452.6 linkuse as main transcriptc.1033G>A p.Glu345Lys missense_variant, splice_region_variant 8/12 ENST00000378553.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAAF1ENST00000378553.10 linkuse as main transcriptc.1033G>A p.Glu345Lys missense_variant, splice_region_variant 8/121 NM_178452.6 P1Q8NEP3-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152268
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152268
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0045
T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.022
Sift
Benign
0.12
T
Sift4G
Benign
0.25
T
Polyphen
0.68
P
Vest4
0.12
MutPred
0.31
Gain of ubiquitination at E345 (P = 0.0011);
MVP
0.26
MPC
0.021
ClinPred
0.59
D
GERP RS
3.6
Varity_R
0.15
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs538389058; hg19: chr16-84203467; API