3-126542213-C-T

Variant summary

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

The NM_152889.3(CHST13):​c.661C>T​(p.His221Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H221Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CHST13
NM_152889.3 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48
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.661C>T p.His221Tyr missense_variant Exon 3 of 3 ENST00000319340.7 NP_690849.1 Q8NET6-1
C3orf22NR_130715.2 linkn.632+7324G>A intron_variant Intron 4 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST13ENST00000319340.7 linkc.661C>T p.His221Tyr missense_variant Exon 3 of 3 1 NM_152889.3 ENSP00000317404.2 Q8NET6-1
C3orf22ENST00000505070.5 linkn.286+7324G>A intron_variant Intron 4 of 5 2 ENSP00000422064.1 Q8N5N4-2

Frequencies

GnomAD3 genomes
AF:
0.0000595
AC:
9
AN:
151342
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000133
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000327
AC:
3
AN:
91828
Hom.:
0
AF XY:
0.0000186
AC XY:
1
AN XY:
53832
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:
0.0000705
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000183
AC:
24
AN:
1309560
Hom.:
0
Cov.:
34
AF XY:
0.0000217
AC XY:
14
AN XY:
646592
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:
0.0000141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000220
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000594
AC:
9
AN:
151450
Hom.:
0
Cov.:
33
AF XY:
0.0000676
AC XY:
5
AN XY:
74014
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000133
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000280
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.661C>T (p.H221Y) alteration is located in exon 3 (coding exon 3) of the CHST13 gene. This alteration results from a C to T substitution at nucleotide position 661, causing the histidine (H) at amino acid position 221 to be replaced by a tyrosine (Y). 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
0.18
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Benign
0.14
Eigen_PC
Benign
0.082
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.87
D
M_CAP
Pathogenic
0.89
D
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.2
L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-2.6
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.017
D
Sift4G
Benign
0.061
T
Polyphen
0.99
D
Vest4
0.19
MutPred
0.47
Loss of disorder (P = 0.0578);
MVP
0.72
MPC
1.8
ClinPred
0.43
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.55

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: rs766907791; hg19: chr3-126261056; API