12-42129785-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173601.2(GXYLT1):c.288G>A(p.Met96Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
GXYLT1
NM_173601.2 missense
NM_173601.2 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 5.03
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16938111).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GXYLT1 | NM_173601.2 | c.288G>A | p.Met96Ile | missense_variant | 2/8 | ENST00000398675.8 | |
GXYLT1 | XM_017019211.1 | c.-241G>A | 5_prime_UTR_variant | 1/8 | |||
GXYLT1 | NM_001099650.2 | c.222-10614G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GXYLT1 | ENST00000398675.8 | c.288G>A | p.Met96Ile | missense_variant | 2/8 | 1 | NM_173601.2 | P4 | |
GXYLT1 | ENST00000280876.6 | c.222-10614G>A | intron_variant | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249372Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135284
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461378Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 727004
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GnomAD4 genome ? Cov.: 32
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?
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32
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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 07, 2021 | The c.288G>A (p.M96I) alteration is located in exon 2 (coding exon 2) of the GXYLT1 gene. This alteration results from a G to A substitution at nucleotide position 288, causing the methionine (M) at amino acid position 96 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of sheet (P = 0.0827);
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