rs1003835285

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014254.3(RXYLT1):​c.1088G>A​(p.Gly363Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RXYLT1
NM_014254.3 missense

Scores

1
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43
Variant links:
Genes affected
RXYLT1 (HGNC:13530): (ribitol xylosyltransferase 1) This gene encodes a type II transmembrane protein that is thought to have glycosyltransferase function. Mutations in this gene result in cobblestone lissencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RXYLT1NM_014254.3 linkuse as main transcriptc.1088G>A p.Gly363Glu missense_variant 6/6 ENST00000261234.11 NP_055069.1 Q9Y2B1
RXYLT1NM_001278237.2 linkuse as main transcriptc.308G>A p.Gly103Glu missense_variant 6/6 NP_001265166.1 Q9Y2B1
RXYLT1XM_047428078.1 linkuse as main transcriptc.779G>A p.Gly260Glu missense_variant 5/5 XP_047284034.1
RXYLT1-AS1NR_126167.1 linkuse as main transcriptn.560C>T non_coding_transcript_exon_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RXYLT1ENST00000261234.11 linkuse as main transcriptc.1088G>A p.Gly363Glu missense_variant 6/61 NM_014254.3 ENSP00000261234.6 Q9Y2B1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251366
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 30, 2021This sequence change replaces glycine with glutamic acid at codon 363 of the RXYLT1 protein (p.Gly363Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RXYLT1-related conditions. 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: "Tolerated"; 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Uncertain
-0.23
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.013
D;T
Sift4G
Benign
0.28
T;D
Polyphen
1.0
D;D
Vest4
0.57
MutPred
0.28
Gain of catalytic residue at S366 (P = 6e-04);.;
MVP
0.076
MPC
0.77
ClinPred
0.98
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.43
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1003835285; hg19: chr12-64202628; API