chr12-42087943-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173601.2(GXYLT1):c.1166C>G(p.Ser389Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000337 in 1,483,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
GXYLT1
NM_173601.2 missense
NM_173601.2 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
GXYLT1 (HGNC:27482): (glucoside xylosyltransferase 1) GXYLT1 is a xylosyltransferase (EC 2.4.2.-) that adds the first xylose to O-glucose-modified residues in the epidermal growth factor (EGF; MIM 131530) repeats of proteins such as NOTCH1 (MIM 190198) (Sethi et al., 2010 [PubMed 19940119]).[supplied by OMIM, Mar 2010]
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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;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2987367).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GXYLT1 | NM_173601.2 | c.1166C>G | p.Ser389Cys | missense_variant | 8/8 | ENST00000398675.8 | |
GXYLT1 | NM_001099650.2 | c.1073C>G | p.Ser358Cys | missense_variant | 7/7 | ||
GXYLT1 | XM_017019211.1 | c.821C>G | p.Ser274Cys | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GXYLT1 | ENST00000398675.8 | c.1166C>G | p.Ser389Cys | missense_variant | 8/8 | 1 | NM_173601.2 | P4 | |
GXYLT1 | ENST00000280876.6 | c.1073C>G | p.Ser358Cys | missense_variant | 7/7 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152060Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000525 AC: 1AN: 190492Hom.: 0 AF XY: 0.00000945 AC XY: 1AN XY: 105826
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GnomAD4 exome AF: 0.00000150 AC: 2AN: 1331532Hom.: 0 Cov.: 22 AF XY: 0.00000151 AC XY: 1AN XY: 662760
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74266
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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 | Feb 13, 2024 | The c.1166C>G (p.S389C) alteration is located in exon 8 (coding exon 8) of the GXYLT1 gene. This alteration results from a C to G substitution at nucleotide position 1166, causing the serine (S) at amino acid position 389 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
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0316);.;
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