17-68450874-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017983.7(WIPI1):c.187G>A(p.Val63Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,104 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
WIPI1
NM_017983.7 missense
NM_017983.7 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 7.45
Genes affected
WIPI1 (HGNC:25471): (WD repeat domain, phosphoinositide interacting 1) This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.814
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WIPI1 | NM_017983.7 | c.187G>A | p.Val63Met | missense_variant | 3/13 | ENST00000262139.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WIPI1 | ENST00000262139.10 | c.187G>A | p.Val63Met | missense_variant | 3/13 | 1 | NM_017983.7 | P1 | |
ENST00000590353.1 | n.173+37079C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249972Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135080
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1460766Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 726714
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74480
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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 | Dec 27, 2023 | The c.187G>A (p.V63M) alteration is located in exon 3 (coding exon 3) of the WIPI1 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
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