16-75479535-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021615.5(CHST6):c.294C>G(p.Ser98Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,612,990 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 111 hom. )

Consequence

CHST6
NM_021615.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.02

Variant links:

Genes affected

CHST6 (HGNC:6938): (carbohydrate sulfotransferase 6) The protein encoded by this gene is an enzyme that catalyzes the transfer of a sulfate group to the GlcNAc residues of keratan. Keratan sulfate helps maintain corneal transparency. Defects in this gene are a cause of macular corneal dystrophy (MCD). [provided by RefSeq, Jan 2010]

CHST6 links:

ENSG00000203472 (HGNC:):

ENSG00000203472 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-75479535-G-C is Benign according to our data. Variant chr16-75479535-G-C is described in ClinVar as [Benign]. Clinvar id is 463681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00687 (1046/152284) while in subpopulation SAS AF= 0.0259 (125/4828). AF 95% confidence interval is 0.0222. There are 10 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST6	NM_021615.5 link	c.294C>G	p.Ser98Ser	synonymous_variant	Exon 3 of 3	ENST00000332272.9	NP_067628.1	Q9GZX3
CHST6	NR_163480.1 link	n.733+2282C>G		intron_variant	Intron 3 of 3
CHST6	NR_163481.1 link	n.577+2282C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST6	ENST00000332272.9 link	c.294C>G	p.Ser98Ser	synonymous_variant	Exon 3 of 3	3	NM_021615.5	ENSP00000328983.4		Q9GZX3

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1046

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00734

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0105

AC:

2608

AN:

249482

Hom.:

AF XY:

0.0115

AC XY:

1559

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.000747

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.000547

Gnomad SAS exome

AF:

0.0259

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.00826

Gnomad OTH exome

AF:

0.00936

GnomAD4 exome

AF:

0.00811

AC:

11853

AN:

1460706

Hom.:

111

Cov.:

AF XY:

0.00875

AC XY:

6357

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.0257

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.00654

Gnomad4 OTH exome

AF:

0.00918

GnomAD4 genome

AF:

0.00687

AC:

1046

AN:

152284

Hom.:

Cov.:

AF XY:

0.00739

AC XY:

550

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.0259

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.00734

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00853

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Macular corneal dystrophy

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CHST6-related disorder

Benign:1

Mar 14, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.032

DANN

Benign

0.83

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