chr2-100393748-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_004854.5(CHST10):​c.568G>C​(p.Asp190His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CHST10
NM_004854.5 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71
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 5 ACMG points.

PM1
In a mutagenesis_site Induces a mild reduction in enzyme activity. (size 0) in uniprot entity CHSTA_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST10NM_004854.5 linkc.568G>C p.Asp190His 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.568G>C p.Asp190His missense_variant Exon 7 of 7 1 NM_004854.5 ENSP00000264249.3 O43529
CHST10ENST00000409701.5 linkc.568G>C p.Asp190His missense_variant Exon 7 of 7 1 ENSP00000387309.1 O43529

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000121
AC:
3
AN:
247782
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134550
show subpopulations
Gnomad AFR exome
AF:
0.000193
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1459186
Hom.:
0
Cov.:
33
AF XY:
0.00000276
AC XY:
2
AN XY:
725904
show subpopulations
Gnomad4 AFR exome
AF:
0.000240
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:
0.0000723
AC:
11
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000808
AC XY:
6
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.000266
Gnomad4 AMR
AF:
0.00
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:
0.0000642
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.568G>C (p.D190H) alteration is located in exon 7 (coding exon 5) of the CHST10 gene. This alteration results from a G to C substitution at nucleotide position 568, causing the aspartic acid (D) at amino acid position 190 to be replaced by a histidine (H). 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
Pathogenic
0.88
BayesDel_addAF
Uncertain
0.021
T
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Benign
0.019
T
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-3.0
D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0010
D;D
Sift4G
Benign
0.16
T;T
Polyphen
0.99
D;D
Vest4
0.75
MVP
0.47
MPC
0.70
ClinPred
0.89
D
GERP RS
6.1
Varity_R
0.67
gMVP
0.86

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: rs368455898; hg19: chr2-101010210; API