3-143121976-C-G

Variant summary

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

The NM_004267.5(CHST2):ā€‹c.1160C>Gā€‹(p.Ala387Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,593,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

CHST2
NM_004267.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50
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=0.39400798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHST2NM_004267.5 linkuse as main transcriptc.1160C>G p.Ala387Gly missense_variant 2/2 ENST00000309575.5 NP_004258.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHST2ENST00000309575.5 linkuse as main transcriptc.1160C>G p.Ala387Gly missense_variant 2/21 NM_004267.5 ENSP00000307911 P1Q9Y4C5-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000128
AC:
3
AN:
233568
Hom.:
0
AF XY:
0.0000158
AC XY:
2
AN XY:
126774
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000281
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1441108
Hom.:
0
Cov.:
31
AF XY:
0.00000699
AC XY:
5
AN XY:
715578
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:
0.0000118
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.0000314
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 13, 2023The c.1160C>G (p.A387G) alteration is located in exon 2 (coding exon 1) of the CHST2 gene. This alteration results from a C to G substitution at nucleotide position 1160, causing the alanine (A) at amino acid position 387 to be replaced by a glycine (G). 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
0.12
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
T
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.39
T
MetaSVM
Uncertain
0.072
D
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.1
N
REVEL
Uncertain
0.34
Sift
Benign
0.035
D
Sift4G
Uncertain
0.028
D
Polyphen
0.98
D
Vest4
0.30
MutPred
0.44
Gain of glycosylation at Y389 (P = 0.0143);
MVP
0.93
MPC
1.5
ClinPred
0.30
T
GERP RS
4.5
Varity_R
0.10
gMVP
0.44

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: rs755171466; hg19: chr3-142840818; API