rs1553342979
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152490.5(B3GALNT2):c.1076G>A(p.Cys359Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
B3GALNT2
NM_152490.5 missense
NM_152490.5 missense
Scores
8
6
4
Clinical Significance
Conservation
PhyloP100: 7.39
Genes affected
B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.863
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
B3GALNT2 | NM_152490.5 | c.1076G>A | p.Cys359Tyr | missense_variant | 9/12 | ENST00000366600.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
B3GALNT2 | ENST00000366600.8 | c.1076G>A | p.Cys359Tyr | missense_variant | 9/12 | 1 | NM_152490.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it in trans with an intronic mutation in a 2-year-old male with global delays, suspected Walker-Warburg muscular dystrophy, hypotonia, contractures, lissencephaly, hypdrocephalus, epliepsy, optic nerve hypoplasia, dysplastic retina, cataract, high myopia, undescended testicles, suspected panhypopituitarism. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2019 | This variant is not present in population databases (ExAC no frequency). 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has been observed in combination with another B3GALNT2 variant in individuals affected with clinical features of muscular dystrophy-dystroglycanopathy (PMID: 25326635, Invitae). ClinVar contains an entry for this variant (Variation ID: 540916). This sequence change replaces cysteine with tyrosine at codon 359 of the B3GALNT2 protein (p.Cys359Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of ubiquitination at K354 (P = 0.0741);
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