4-48991998-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_025087.3(CWH43):āc.419A>Gā(p.Tyr140Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000023 ( 0 hom. )
Consequence
CWH43
NM_025087.3 missense
NM_025087.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.24
Genes affected
CWH43 (HGNC:26133): (cell wall biogenesis 43 C-terminal homolog) Predicted to be involved in GPI anchor biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CWH43 | NM_025087.3 | c.419A>G | p.Tyr140Cys | missense_variant | 4/16 | ENST00000226432.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CWH43 | ENST00000226432.9 | c.419A>G | p.Tyr140Cys | missense_variant | 4/16 | 1 | NM_025087.3 | P1 | |
CWH43 | ENST00000513409.1 | c.338A>G | p.Tyr113Cys | missense_variant | 4/16 | 2 | |||
CWH43 | ENST00000514053.6 | c.419A>G | p.Tyr140Cys | missense_variant, NMD_transcript_variant | 4/14 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251380Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135858
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461500Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727064
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74488
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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 | May 01, 2023 | The c.419A>G (p.Y140C) alteration is located in exon 4 (coding exon 4) of the CWH43 gene. This alteration results from a A to G substitution at nucleotide position 419, causing the tyrosine (Y) at amino acid position 140 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of sheet (P = 0.0457);.;
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