NM_001491.3:c.330G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001491.3(GCNT2):​c.330G>C​(p.Arg110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R110R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GCNT2
NM_001491.3 missense

Scores

3
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157
Variant links:
Genes affected
GCNT2 (HGNC:4204): (glucosaminyl (N-acetyl) transferase 2 (I blood group)) This gene encodes the enzyme responsible for formation of the blood group I antigen. The i and I antigens are distinguished by linear and branched poly-N-acetyllactosaminoglycans, respectively. The encoded protein is the I-branching enzyme, a beta-1,6-N-acetylglucosaminyltransferase responsible for the conversion of fetal i antigen to adult I antigen in erythrocytes during embryonic development. Mutations in this gene have been associated with adult i blood group phenotype. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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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, 0.906

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GCNT2NM_001491.3 linkc.330G>C p.Arg110Ser missense_variant Exon 1 of 3 ENST00000316170.9 NP_001482.1 Q8N0V5-2
GCNT2NM_145649.5 linkc.925+26917G>C intron_variant Intron 3 of 4 ENST00000495262.7 NP_663624.1 Q8N0V5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCNT2ENST00000316170.9 linkc.330G>C p.Arg110Ser missense_variant Exon 1 of 3 1 NM_001491.3 ENSP00000314844.3 Q8N0V5-2
GCNT2ENST00000495262.7 linkc.925+26917G>C intron_variant Intron 3 of 4 2 NM_145649.5 ENSP00000419411.2 Q8N0V5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461790
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
13
DANN
Uncertain
1.0
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Benign
0.020
T
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Benign
-0.97
T
PROVEAN
Pathogenic
-5.2
D;.
REVEL
Uncertain
0.33
Sift4G
Uncertain
0.0020
D;.
Vest4
0.86
MutPred
0.82
Loss of methylation at R110 (P = 0.0281);Loss of methylation at R110 (P = 0.0281);
MVP
0.59
ClinPred
0.88
D
GERP RS
2.7

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-10556986; API