chr16-17109015-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022166.4(XYLT1):c.2560G>A(p.Glu854Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E854A) has been classified as Likely benign.
Frequency
Consequence
NM_022166.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XYLT1 | NM_022166.4 | c.2560G>A | p.Glu854Lys | missense_variant, splice_region_variant | 12/12 | ENST00000261381.7 | |
XYLT1 | XM_047434458.1 | c.2521G>A | p.Glu841Lys | missense_variant, splice_region_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XYLT1 | ENST00000261381.7 | c.2560G>A | p.Glu854Lys | missense_variant, splice_region_variant | 12/12 | 1 | NM_022166.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000110 AC: 2AN: 181890Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 95564
GnomAD4 exome AF: 7.39e-7 AC: 1AN: 1353524Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 659680
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Desbuquois dysplasia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 01, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1407331). This variant has not been reported in the literature in individuals affected with XYLT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 854 of the XYLT1 protein (p.Glu854Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at