16-75473355-T-A

Variant names:

• chr16-75473355-T-A
• rs9923834
• NM_021615.5:c.*5286A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021615.5(CHST6):​c.*5286A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 151,986 control chromosomes in the GnomAD database, including 52,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (51949 hom., cov: 29)
  • Exomes 𝑓: 0.84 (73 hom.)
• Consequence: CHST6 NM_021615.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877
• Publications: 12 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-75473355-T-A is Benign according to our data. Variant chr16-75473355-T-A is described in ClinVar as Benign. ClinVar VariationId is 320507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST6	NM_021615.5	MANE Select	c.*5286A>T		3_prime_UTR	Exon 3 of 3	NP_067628.1	Q9GZX3
	CHST6	NR_163480.1		n.846A>T		non_coding_transcript_exon	Exon 4 of 4
	CHST6	NR_163481.1		n.690A>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST6	ENST00000332272.9	TSL:3 MANE Select	c.*5286A>T		3_prime_UTR	Exon 3 of 3	ENSP00000328983.4	Q9GZX3
	CHST6	ENST00000649824.1		n.*711A>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000496806.1	Q9GZX3
	CHST6	ENST00000649824.1		n.*711A>T		3_prime_UTR	Exon 4 of 4	ENSP00000496806.1	Q9GZX3

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125292 AN: 151666 Hom.: 51897 Cov.: 29

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.837 AC: 169 AN: 202 Hom.: 73 Cov.: 0 AF XY: 0.831 AC XY: 133 AN XY: 160

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.860 AC: 148 AN: 172

Other (OTH) AF: 1.00 AC: 8 AN: 8

GnomAD4 genome AF: 0.826 AC: 125400 AN: 151784 Hom.: 51949 Cov.: 29 AF XY: 0.826 AC XY: 61219 AN XY: 74136

African (AFR) AF: 0.794 AC: 32819 AN: 41342

American (AMR) AF: 0.849 AC: 12943 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3094 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3213 AN: 5108

South Asian (SAS) AF: 0.860 AC: 4152 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8528 AN: 10512

Middle Eastern (MID) AF: 0.908 AC: 265 AN: 292

European-Non Finnish (NFE) AF: 0.851 AC: 57856 AN: 67976

Other (OTH) AF: 0.838 AC: 1769 AN: 2110

Alfa AF: 0.818 Hom.: 2579

Bravo AF: 0.825

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Macular corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.94
DANN	Benign	0.67
PhyloP100		-0.88

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: rs9923834; hg19: chr16-75507253;