Genetic Variant CHST7:p.Pro182Arg (chrX-46574476-C-G) – ACMG Classification: Likely_benign (-5 pts)

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

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]

CHST7 links:

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
CHST7	NM_019886.4 link	c.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
CHST7	ENST00000276055.4 link	c.545C>G	p.Pro182Arg	missense_variant	Exon 1 of 2	1	NM_019886.4	ENSP00000276055.3		Q9NS84

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

112588

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

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:

AN:

166241

Hom.:

AF XY:

0.0000847

AC XY:

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.:

Cov.:

AF XY:

0.0000945

AC XY:

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:

AN:

112588

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

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.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000838

AC:

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

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.39

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.74

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

Sift4G

Benign

0.67

Polyphen

0.90

Vest4

0.26

MVP

0.91

ClinPred

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over