16-75473355-T-A

Position:

• chr16-75473355-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST6	NM_021615.5	c.*5286A>T		3_prime_UTR_variant	3/3	ENST00000332272.9
CHST6	NR_163480.1	n.846A>T		non_coding_transcript_exon_variant	4/4
CHST6	NR_163481.1	n.690A>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST6	ENST00000332272.9	c.*5286A>T		3_prime_UTR_variant	3/3	3	NM_021615.5	P1
CHST6	ENST00000649824.1	c.*711A>T		3_prime_UTR_variant, NMD_transcript_variant	4/4
CHST6	ENST00000649341.1			downstream_gene_variant

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

Gnomad4 AFR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.860

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.838

Alfa AF: 0.818 Hom.: 2579

Bravo AF: 0.825

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Macular corneal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs9923834; hg19: chr16-75507253;