3-143120920-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004267.5(CHST2):​c.104G>C​(p.Arg35Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 151,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CHST2
NM_004267.5 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74
Variant links:
Genes affected
CHST2 (HGNC:1970): (carbohydrate sulfotransferase 2) This locus encodes a sulfotransferase protein. The encoded enzyme catalyzes the sulfation of a nonreducing N-acetylglucosamine residue, and may play a role in biosynthesis of 6-sulfosialyl Lewis X antigen. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3608012).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST2NM_004267.5 linkc.104G>C p.Arg35Pro missense_variant Exon 2 of 2 ENST00000309575.5 NP_004258.2 Q9Y4C5-1V9HVX9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST2ENST00000309575.5 linkc.104G>C p.Arg35Pro missense_variant Exon 2 of 2 1 NM_004267.5 ENSP00000307911.3 Q9Y4C5-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151960
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1361426
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
671706
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151960
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000197
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:
0.00
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.104G>C (p.R35P) alteration is located in exon 2 (coding exon 1) of the CHST2 gene. This alteration results from a G to C substitution at nucleotide position 104, causing the arginine (R) at amino acid position 35 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.24
T
Eigen
Benign
0.048
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.57
T
M_CAP
Pathogenic
0.81
D
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
0.032
D
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
-0.65
N
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.86
P
Vest4
0.31
MutPred
0.22
Loss of glycosylation at P37 (P = 0.0035);
MVP
0.89
MPC
1.4
ClinPred
0.56
D
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.39
gMVP
0.50

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: rs757732659; hg19: chr3-142839762; API