X-46574476-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_019886.4(CHST7):​c.545C>G​(p.Pro182Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000954 in 1,205,389 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000092 ( 0 hom. 34 hem. )

Consequence

CHST7
NM_019886.4 missense

Scores

4
2
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20
Variant links:
Genes affected
CHST7 (HGNC:13817): (carbohydrate sulfotransferase 7) This gene is a member of the Gal/GalNAc/GlcNAc (galactose/N-acetylgalactosamine/N-acetylglucosamine) 6-O-sulfotransferase (GST) family. Members of this family encode enzymes that catalyze the specific addition of sulfate groups to distinct hydroxyl and amino groups of carbohydrates. The encoded protein catalyzes the sulfation of 6-hydroxyl group of GalNAc in chondroitin. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39458185).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST7NM_019886.4 linkc.545C>G p.Pro182Arg missense_variant Exon 1 of 2 ENST00000276055.4 NP_063939.2 Q9NS84

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST7ENST00000276055.4 linkc.545C>G p.Pro182Arg missense_variant Exon 1 of 2 1 NM_019886.4 ENSP00000276055.3 Q9NS84

Frequencies

GnomAD3 genomes
AF:
0.000133
AC:
15
AN:
112588
Hom.:
0
Cov.:
24
AF XY:
0.0000575
AC XY:
2
AN XY:
34792
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:
0.000282
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000102
AC:
17
AN:
166241
Hom.:
0
AF XY:
0.0000847
AC XY:
5
AN XY:
59007
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:
0.000234
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000915
AC:
100
AN:
1092801
Hom.:
0
Cov.:
32
AF XY:
0.0000945
AC XY:
34
AN XY:
359801
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:
0.0000512
Gnomad4 NFE exome
AF:
0.000114
Gnomad4 OTH exome
AF:
0.0000436
GnomAD4 genome
AF:
0.000133
AC:
15
AN:
112588
Hom.:
0
Cov.:
24
AF XY:
0.0000575
AC XY:
2
AN XY:
34792
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:
0.000282
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00103
Hom.:
5
Bravo
AF:
0.000128
ExAC
AF:
0.0000838
AC:
10

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.545C>G (p.P182R) alteration is located in exon 1 (coding exon 1) of the CHST7 gene. This alteration results from a C to G substitution at nucleotide position 545, causing the proline (P) at amino acid position 182 to be replaced by an arginine (R). 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
0.077
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.090
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
FATHMM_MKL
Benign
0.50
N
LIST_S2
Benign
0.50
T
M_CAP
Pathogenic
0.84
D
MetaRNN
Benign
0.39
T
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.74
N
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.67
T
Polyphen
0.90
P
Vest4
0.26
MVP
0.91
ClinPred
0.17
T
GERP RS
4.0
Varity_R
0.39
gMVP
0.82

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: rs752917425; hg19: chrX-46433911; COSMIC: COSV99034734; API