dbSNP rs118144424: CHST6:p.Ser98Ser (chr16-75479535-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

macular corneal dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

CHST6 links:

ENSG00000203472 (HGNC:):

ENSG00000203472 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021615.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST6	NM_021615.5	MANE Select	c.294C>G	p.Ser98Ser	synonymous	Exon 3 of 3	NP_067628.1	Q9GZX3
CHST6	NR_163480.1		n.733+2282C>G		intron	N/A
CHST6	NR_163481.1		n.577+2282C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST6	ENST00000332272.9	TSL:3 MANE Select	c.294C>G	p.Ser98Ser	synonymous	Exon 3 of 3	ENSP00000328983.4	Q9GZX3
CHST6	ENST00000390664.3	TSL:1	c.294C>G	p.Ser98Ser	synonymous	Exon 4 of 4	ENSP00000375079.2	Q9GZX3
CHST6	ENST00000970639.1		c.294C>G	p.Ser98Ser	synonymous	Exon 3 of 3	ENSP00000640698.1

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

GnomAD2 exomes

AF:

0.0105

AC:

2608

AN:

249482

AF XY:

0.0115

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 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

African (AFR)

AF:

0.000896

AC:

AN:

33466

American (AMR)

AF:

0.00277

AC:

124

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

672

AN:

26118

East Asian (EAS)

AF:

0.000202

AC:

AN:

39692

South Asian (SAS)

AF:

0.0252

AC:

2170

AN:

86256

European-Finnish (FIN)

AF:

0.0187

AC:

978

AN:

52438

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00654

AC:

7269

AN:

1111874

Other (OTH)

AF:

0.00918

AC:

554

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

974

1947

2921

3894

4868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00687

AC:

1046

AN:

152284

Hom.:

Cov.:

AF XY:

0.00739

AC XY:

550

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41578

American (AMR)

AF:

0.00320

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3468

East Asian (EAS)

AF:

0.000968

AC:

AN:

5166

South Asian (SAS)

AF:

0.0259

AC:

125

AN:

4828

European-Finnish (FIN)

AF:

0.0175

AC:

186

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00734

AC:

499

AN:

68014

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Macular corneal dystrophy (2)

CHST6-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.032

(source)

DANN

Benign

0.83

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over