chr3-58410115-A-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_017771.5(PXK):c.1421A>T(p.Asn474Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,601,568 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0052 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0070 ( 138 hom. )
Consequence
PXK
NM_017771.5 missense
NM_017771.5 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 3.46
Genes affected
PXK (HGNC:23326): (PX domain containing serine/threonine kinase like) This gene encodes a phox (PX) domain-containing protein which may be involved in synaptic transmission and the ligand-induced internalization and degradation of epidermal growth factors. Variations in this gene may be associated with susceptibility to systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0034009814).
BP6
?
Variant 3-58410115-A-T is Benign according to our data. Variant chr3-58410115-A-T is described in ClinVar as [Benign]. Clinvar id is 771351.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00519 (790/152254) while in subpopulation SAS AF= 0.0402 (194/4822). AF 95% confidence interval is 0.0356. There are 9 homozygotes in gnomad4. There are 405 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PXK | NM_017771.5 | c.1421A>T | p.Asn474Ile | missense_variant | 16/18 | ENST00000356151.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PXK | ENST00000356151.7 | c.1421A>T | p.Asn474Ile | missense_variant | 16/18 | 1 | NM_017771.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00523 AC: 796AN: 152136Hom.: 9 Cov.: 32
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?
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796
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GnomAD3 exomes AF: 0.00929 AC: 2333AN: 251154Hom.: 38 AF XY: 0.0113 AC XY: 1540AN XY: 135758
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GnomAD4 exome AF: 0.00703 AC: 10191AN: 1449314Hom.: 138 Cov.: 29 AF XY: 0.00831 AC XY: 6001AN XY: 721874
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GnomAD4 genome ? AF: 0.00519 AC: 790AN: 152254Hom.: 9 Cov.: 32 AF XY: 0.00544 AC XY: 405AN XY: 74450
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ESP6500AA
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ESP6500EA
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77
ExAC
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1211
Asia WGS
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AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.;.;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;D;D;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;.;L;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;N;N;N;N;.;D
REVEL
Benign
Sift
Benign
T;.;.;T;T;T;D;.;.
Sift4G
Benign
T;T;T;T;T;T;T;T;D
Polyphen
B;.;B;B;.;B;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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