16-75479345-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021615.5(CHST6):c.484C>G(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,612,722 control chromosomes in the GnomAD database, including 2,321 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 137 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2184 hom. )

Consequence

CHST6
NM_021615.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.41

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051915944).

BP6

Variant 16-75479345-G-C is Benign according to our data. Variant chr16-75479345-G-C is described in ClinVar as [Benign]. Clinvar id is 320611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-75479345-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST6	NM_021615.5 link	c.484C>G	p.Arg162Gly	missense_variant	Exon 3 of 3	ENST00000332272.9	NP_067628.1	Q9GZX3
CHST6	NR_163480.1 link	n.733+2472C>G		intron_variant	Intron 3 of 3
CHST6	NR_163481.1 link	n.577+2472C>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.484C>G	p.Arg162Gly	missense_variant	Exon 3 of 3	3	NM_021615.5	ENSP00000328983.4		Q9GZX3

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5396

AN:

152214

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0551

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0352

AC:

8681

AN:

246334

Hom.:

220

AF XY:

0.0349

AC XY:

4680

AN XY:

134046

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00628

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.0559

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0509

AC:

74388

AN:

1460390

Hom.:

2184

Cov.:

AF XY:

0.0496

AC XY:

36028

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.00876

Gnomad4 AMR exome

AF:

0.0241

Gnomad4 ASJ exome

AF:

0.0532

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00671

Gnomad4 FIN exome

AF:

0.0340

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0492

GnomAD4 genome

AF:

0.0354

AC:

5397

AN:

152332

Hom.:

137

Cov.:

AF XY:

0.0322

AC XY:

2400

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.0551

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0257

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0381

Hom.:

Bravo

AF:

0.0367

TwinsUK

AF:

0.0585

AC:

217

ALSPAC

AF:

0.0638

AC:

246

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.0529

AC:

454

ExAC

AF:

0.0350

AC:

4243

EpiCase

AF:

0.0595

EpiControl

AF:

0.0607

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Macular corneal dystrophy

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jan 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

D;D;D

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.28

.;.;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

0.34

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

N;.;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.018

D;.;D

Sift4G

Uncertain

0.044

D;.;D

Polyphen

0.0

B;B;B

Vest4

0.015

MPC

0.41

ClinPred

0.013

GERP RS

2.5

Varity_R

0.12

gMVP

0.92

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