chr3-195270666-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152531.5(XXYLT1):c.393C>G(p.Phe131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,582,472 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
XXYLT1
NM_152531.5 missense
NM_152531.5 missense
Scores
2
2
15
Clinical Significance
Conservation
PhyloP100: 2.02
Genes affected
XXYLT1 (HGNC:26639): (xyloside xylosyltransferase 1) Enables magnesium ion binding activity; manganese ion binding activity; and xylosyl alpha-1,3-xylosyltransferase activity. Involved in O-glycan processing. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.08235893).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XXYLT1 | NM_152531.5 | c.393C>G | p.Phe131Leu | missense_variant | 1/4 | ENST00000310380.11 | |
XXYLT1 | XM_017005749.3 | c.393C>G | p.Phe131Leu | missense_variant | 1/4 | ||
XXYLT1 | XR_924105.4 | n.494C>G | non_coding_transcript_exon_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XXYLT1 | ENST00000310380.11 | c.393C>G | p.Phe131Leu | missense_variant | 1/4 | 1 | NM_152531.5 | P1 | |
XXYLT1 | ENST00000455281.1 | c.198C>G | p.Phe66Leu | missense_variant, NMD_transcript_variant | 1/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000140 AC: 2AN: 1430180Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1AN XY: 711324
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74470
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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 11, 2022 | The c.393C>G (p.F131L) alteration is located in exon 1 (coding exon 1) of the XXYLT1 gene. This alteration results from a C to G substitution at nucleotide position 393, causing the phenylalanine (F) at amino acid position 131 to be replaced by a leucine (L). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of helix (P = 0.0093);
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