16-75479535-G-C

Variant names:

• chr16-75479535-G-C
• rs118144424
• NM_021615.5:c.294C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.02
• Publications: 6 publications found

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000203472 (HGNC:):

ACMG classification

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

Selected	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
	CHST6	NR_163480.1		n.733+2282C>G		intron	N/A
	CHST6	NR_163481.1		n.577+2282C>G		intron	N/A

Ensembl Transcripts

Selected	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
	CHST6	ENST00000390664.3	TSL:1	c.294C>G	p.Ser98Ser	synonymous	Exon 4 of 4	ENSP00000375079.2
	CHST6	ENST00000649341.1		n.294C>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000497635.1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152166 Hom.: 10 Cov.: 33

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

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.: 32 AF XY: 0.00875 AC XY: 6357 AN XY: 726684

African (AFR) AF: 0.000896 AC: 30 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: 8 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: 48 AN: 5768

European-Non Finnish (NFE) AF: 0.00654 AC: 7269 AN: 1111874

Other (OTH) AF: 0.00918 AC: 554 AN: 60376

GnomAD4 genome AF: 0.00687 AC: 1046 AN: 152284 Hom.: 10 Cov.: 33 AF XY: 0.00739 AC XY: 550 AN XY: 74460

African (AFR) AF: 0.00113 AC: 47 AN: 41578

American (AMR) AF: 0.00320 AC: 49 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3468

East Asian (EAS) AF: 0.000968 AC: 5 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: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00734 AC: 499 AN: 68014

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00853 Hom.: 6

Bravo AF: 0.00497

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00699

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Macular corneal dystrophy (2)
-	-	1	CHST6-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.032
DANN	Benign	0.83
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs118144424; hg19: chr16-75513433;