chr16-74887695-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_030581.4(WDR59):c.2407G>T(p.Gly803Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,082 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 42 hom. )
Consequence
WDR59
NM_030581.4 missense
NM_030581.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 1.45
Genes affected
WDR59 (HGNC:25706): (WD repeat domain 59) Involved in cellular response to amino acid starvation and positive regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.009161562).
BP6
?
Variant 16-74887695-C-A is Benign according to our data. Variant chr16-74887695-C-A is described in ClinVar as [Benign]. Clinvar id is 785539.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1881/152272) while in subpopulation AFR AF= 0.043 (1784/41528). AF 95% confidence interval is 0.0413. There are 42 homozygotes in gnomad4. There are 875 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 42 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR59 | NM_030581.4 | c.2407G>T | p.Gly803Cys | missense_variant | 23/26 | ENST00000262144.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR59 | ENST00000262144.11 | c.2407G>T | p.Gly803Cys | missense_variant | 23/26 | 5 | NM_030581.4 | P1 | |
WDR59 | ENST00000563797.5 | c.352G>T | p.Gly118Cys | missense_variant | 4/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0124 AC: 1881AN: 152154Hom.: 42 Cov.: 32
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GnomAD3 exomes AF: 0.00315 AC: 790AN: 251102Hom.: 15 AF XY: 0.00231 AC XY: 313AN XY: 135748
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GnomAD4 exome AF: 0.00120 AC: 1751AN: 1461810Hom.: 42 Cov.: 30 AF XY: 0.00101 AC XY: 731AN XY: 727220
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GnomAD4 genome ? AF: 0.0124 AC: 1881AN: 152272Hom.: 42 Cov.: 32 AF XY: 0.0117 AC XY: 875AN XY: 74484
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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 | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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