16-75529687-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024533.5(CHST5):​c.698G>A​(p.Arg233Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,140 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: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CHST5
NM_024533.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79
Variant links:
Genes affected
CHST5 (HGNC:1973): (carbohydrate sulfotransferase 5) The protein encoded by this gene belongs to the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family, members of which catalyze the transfer of sulfate to position 6 of galactose (Gal), N-acetylgalactosamine (GalNAc), or N-acetylglucosamine (GlcNAc) residues within proteoglycans, and sulfation of O-linked sugars of mucin-type acceptors. Carbohydrate sulfation plays a critical role in many biologic processes. This gene is predominantly expressed in colon and small intestine. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST5NM_024533.5 linkc.698G>A p.Arg233Gln missense_variant Exon 4 of 4 ENST00000336257.8 NP_078809.2 Q9GZS9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST5ENST00000336257.8 linkc.698G>A p.Arg233Gln missense_variant Exon 4 of 4 1 NM_024533.5 ENSP00000338783.3 Q9GZS9-1
ENSG00000260092ENST00000460606.1 linkn.*797G>A non_coding_transcript_exon_variant Exon 5 of 5 1 ENSP00000457544.1 H3BUA1
ENSG00000260092ENST00000460606.1 linkn.*797G>A 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000457544.1 H3BUA1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458140
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
725202
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.698G>A (p.R233Q) alteration is located in exon 3 (coding exon 1) of the CHST5 gene. This alteration results from a G to A substitution at nucleotide position 698, causing the arginine (R) at amino acid position 233 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.78
D
Eigen
Uncertain
0.42
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.020
T
MetaRNN
Pathogenic
0.98
D
MetaSVM
Benign
-0.68
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0060
D
Polyphen
1.0
D
Vest4
0.77
MutPred
0.90
Loss of methylation at R233 (P = 0.0104);
MVP
0.55
MPC
1.6
ClinPred
0.99
D
GERP RS
2.8
Varity_R
0.84
gMVP
0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75563585; API