chr4-3463424-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173660.5(DOK7):c.49A>C(p.Lys17Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000705 in 141,892 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: 𝑓 0.0000070 ( 0 hom., cov: 30)
Consequence
DOK7
NM_173660.5 missense
NM_173660.5 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 3.05
Genes affected
DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
Genome browser will be placed here
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=0.42211884).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.49A>C | p.Lys17Gln | missense_variant | 1/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.49A>C | p.Lys17Gln | missense_variant | 1/7 | 1 | NM_173660.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000705 AC: 1AN: 141892Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
1
AN:
141892
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Cov.: 45
GnomAD4 exome
Cov.:
45
GnomAD4 genome ? AF: 0.00000705 AC: 1AN: 141892Hom.: 0 Cov.: 30 AF XY: 0.0000146 AC XY: 1AN XY: 68724
GnomAD4 genome
?
AF:
AC:
1
AN:
141892
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
68724
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DOK7 protein function. ClinVar contains an entry for this variant (Variation ID: 1053781). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 17 of the DOK7 protein (p.Lys17Gln). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;.
Polyphen
0.97
.;D;.
Vest4
MutPred
Gain of glycosylation at S21 (P = 0.0131);Gain of glycosylation at S21 (P = 0.0131);Gain of glycosylation at S21 (P = 0.0131);
MVP
MPC
0.0044
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at