chr13-98829429-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001366683.2(DOCK9):c.4843C>A(p.Pro1615Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 0 hom. )
Consequence
DOCK9
NM_001366683.2 missense
NM_001366683.2 missense
Scores
7
4
2
Clinical Significance
Conservation
PhyloP100: 9.50
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DOCK9. . Gene score misZ 3.0983 (greater than the threshold 3.09). Trascript score misZ 3.4483 (greater than threshold 3.09). GenCC has associacion of gene with keratoconus.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.865
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK9 | NM_001366683.2 | c.4843C>A | p.Pro1615Thr | missense_variant | 43/53 | ENST00000682017.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK9 | ENST00000682017.1 | c.4843C>A | p.Pro1615Thr | missense_variant | 43/53 | NM_001366683.2 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249056Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135128
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GnomAD4 exome AF: 0.0000965 AC: 141AN: 1461652Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 727110
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.4777C>A (p.P1593T) alteration is located in exon 43 (coding exon 43) of the DOCK9 gene. This alteration results from a C to A substitution at nucleotide position 4777, causing the proline (P) at amino acid position 1593 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
1.0, 1.0
.;D;.;D
Vest4
0.92, 0.88
MVP
MPC
1.1
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at