rs587777436
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_005660.3(SLC35A2):c.638C>T(p.Ser213Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
SLC35A2
NM_005660.3 missense
NM_005660.3 missense
Scores
13
3
1
Clinical Significance
Conservation
PhyloP100: 5.79
Genes affected
SLC35A2 (HGNC:11022): (solute carrier family 35 member A2) This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
In a mutagenesis_site No effect on localization to Golgi apparatus. (size 0) in uniprot entity S35A2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954
PP5
Variant X-48905271-G-A is Pathogenic according to our data. Variant chrX-48905271-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 135676.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC35A2 | NM_005660.3 | c.638C>T | p.Ser213Phe | missense_variant | 4/5 | ENST00000247138.11 | NP_005651.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC35A2 | ENST00000247138.11 | c.638C>T | p.Ser213Phe | missense_variant | 4/5 | 1 | NM_005660.3 | ENSP00000247138.5 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1085382Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 353252
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1085382
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
353252
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
SLC35A2-congenital disorder of glycosylation Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;D;.;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;.;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;.
Polyphen
D;D;.;D;.;.
Vest4
MutPred
Loss of glycosylation at S213 (P = 0.0138);Loss of glycosylation at S213 (P = 0.0138);.;.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at