2-100393318-C-T

Variant summary

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

The NM_004854.5(CHST10):​c.998G>A​(p.Arg333Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CHST10
NM_004854.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04
Variant links:
Genes affected
CHST10 (HGNC:19650): (carbohydrate sulfotransferase 10) This protein encoded by this gene transfers sulfate to the C-3 hydroxyl of terminal glucuronic acid of protein- and lipid-linked oligosaccharides. This protein was first identified as a sulfotransferase that acts on the human natural killer-1 (HNK-1) glycan; HNK-1 is a carbohydrate involved in neurodevelopment and synaptic plasticity.[provided by RefSeq, Feb 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=0.38224763).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST10NM_004854.5 linkc.998G>A p.Arg333Gln missense_variant Exon 7 of 7 ENST00000264249.8 NP_004845.1 O43529

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST10ENST00000264249.8 linkc.998G>A p.Arg333Gln missense_variant Exon 7 of 7 1 NM_004854.5 ENSP00000264249.3 O43529
CHST10ENST00000409701.5 linkc.998G>A p.Arg333Gln missense_variant Exon 7 of 7 1 ENSP00000387309.1 O43529

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251490
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 08, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.998G>A (p.R333Q) alteration is located in exon 7 (coding exon 5) of the CHST10 gene. This alteration results from a G to A substitution at nucleotide position 998, causing the arginine (R) at amino acid position 333 to be replaced by a glutamine (Q). 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
0.087
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
.;D
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
0.73
N;N
REVEL
Uncertain
0.38
Sift
Benign
0.67
T;T
Sift4G
Benign
0.20
T;T
Polyphen
1.0
D;D
Vest4
0.52
MutPred
0.58
Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);
MVP
0.82
MPC
0.87
ClinPred
0.23
T
GERP RS
5.9
Varity_R
0.17
gMVP
0.68

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: rs756945972; hg19: chr2-101009780; API