rs150422575
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_000147.5(FUCA1):c.1274G>A(p.Gly425Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
FUCA1
NM_000147.5 missense
NM_000147.5 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 5.45
Genes affected
FUCA1 (HGNC:4006): (alpha-L-fucosidase 1) The protein encoded by this gene is a lysosomal enzyme involved in the degradation of fucose-containing glycoproteins and glycolipids. Mutations in this gene are associated with fucosidosis (FUCA1D), which is an autosomal recessive lysosomal storage disease. A pseudogene of this locus is present on chr 2.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000361 (55/152242) while in subpopulation AFR AF= 0.0012 (50/41528). AF 95% confidence interval is 0.000938. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUCA1 | NM_000147.5 | c.1274G>A | p.Gly425Glu | missense_variant | 8/8 | ENST00000374479.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUCA1 | ENST00000374479.4 | c.1274G>A | p.Gly425Glu | missense_variant | 8/8 | 1 | NM_000147.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000362 AC: 55AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251356Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135846
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GnomAD4 exome AF: 0.0000622 AC: 91AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38AN XY: 727234
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GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74440
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fucosidosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 425 of the FUCA1 protein (p.Gly425Glu). This variant is present in population databases (rs150422575, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FUCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 456362). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
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