rs763247584

Variant summary

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

The NM_018413.6(CHST11):​c.655C>G​(p.Arg219Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R219C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CHST11
NM_018413.6 missense

Scores

9
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
CHST11 (HGNC:17422): (carbohydrate sulfotransferase 11) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. A chromosomal translocation involving this gene and IgH, t(12;14)(q23;q32), has been reported in a patient with B-cell chronic lymphocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

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, 0.853

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST11NM_018413.6 linkc.655C>G p.Arg219Gly missense_variant Exon 3 of 3 ENST00000303694.6 NP_060883.1 Q9NPF2-1A0A024RBL0
CHST11NM_001173982.2 linkc.640C>G p.Arg214Gly missense_variant Exon 3 of 3 NP_001167453.1 Q9NPF2-2
CHST11XM_047428914.1 linkc.418C>G p.Arg140Gly missense_variant Exon 2 of 2 XP_047284870.1
CHST11XM_047428915.1 linkc.418C>G p.Arg140Gly missense_variant Exon 2 of 2 XP_047284871.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST11ENST00000303694.6 linkc.655C>G p.Arg219Gly missense_variant Exon 3 of 3 1 NM_018413.6 ENSP00000305725.5 Q9NPF2-1
CHST11ENST00000549260.5 linkc.640C>G p.Arg214Gly missense_variant Exon 3 of 3 1 ENSP00000450004.1 Q9NPF2-2
CHST11ENST00000549016.1 linkc.*60C>G downstream_gene_variant 4 ENSP00000449095.1 F8VXK3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
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
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
.;D
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.077
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
0.048
D
MutationAssessor
Uncertain
2.7
.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.79
MutPred
0.67
.;Loss of methylation at K215 (P = 0.0557);
MVP
0.93
MPC
1.9
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.72
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-105151177; API