chr3-126542215-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152889.3(CHST13):​c.663C>A​(p.His221Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,322,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H221Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

CHST13
NM_152889.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148
Variant links:
Genes affected
CHST13 (HGNC:21755): (carbohydrate sulfotransferase 13) 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 the C4 hydroxyl of beta-1,4-linked N-acetylgalactosamine (GalNAc) flanked by glucuronic acid residue in chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. [provided by RefSeq, Aug 2011]
C3orf22 (HGNC:28534): (chromosome 3 open reading frame 22)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST13NM_152889.3 linkc.663C>A p.His221Gln missense_variant Exon 3 of 3 ENST00000319340.7 NP_690849.1 Q8NET6-1
C3orf22NR_130715.2 linkn.632+7322G>T intron_variant Intron 4 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST13ENST00000319340.7 linkc.663C>A p.His221Gln missense_variant Exon 3 of 3 1 NM_152889.3 ENSP00000317404.2 Q8NET6-1
C3orf22ENST00000505070.5 linkn.286+7322G>T intron_variant Intron 4 of 5 2 ENSP00000422064.1 Q8N5N4-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000378
AC:
5
AN:
1322838
Hom.:
0
Cov.:
34
AF XY:
0.00000306
AC XY:
2
AN XY:
653842
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:
0.0000412
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.50e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000186
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.663C>A (p.H221Q) alteration is located in exon 3 (coding exon 3) of the CHST13 gene. This alteration results from a C to A substitution at nucleotide position 663, causing the histidine (H) at amino acid position 221 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
0.20
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
23
DANN
Benign
0.96
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.083
Eigen_PC
Benign
-0.0011
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.79
T
M_CAP
Pathogenic
0.91
D
MetaRNN
Uncertain
0.49
T
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.24
Sift
Benign
0.030
D
Sift4G
Benign
0.11
T
Polyphen
0.96
D
Vest4
0.15
MutPred
0.40
Gain of solvent accessibility (P = 0.0074);
MVP
0.78
MPC
1.7
ClinPred
0.58
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.51

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: rs754370173; hg19: chr3-126261058; API