16-75473176-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_021615.5(CHST6):c.*5465C>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 0.000453 in 152,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CHST6
NM_021615.5 3_prime_UTR
NM_021615.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.816
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 16-75473176-G-A is Benign according to our data. Variant chr16-75473176-G-A is described in ClinVar as [Benign]. Clinvar id is 320503.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000453 (69/152336) while in subpopulation SAS AF= 0.0139 (67/4828). AF 95% confidence interval is 0.0112. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHST6 | NM_021615.5 | c.*5465C>T | 3_prime_UTR_variant | 3/3 | ENST00000332272.9 | ||
CHST6 | NR_163480.1 | n.1025C>T | non_coding_transcript_exon_variant | 4/4 | |||
CHST6 | NR_163481.1 | n.869C>T | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHST6 | ENST00000332272.9 | c.*5465C>T | 3_prime_UTR_variant | 3/3 | 3 | NM_021615.5 | P1 | ||
CHST6 | ENST00000649824.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152218Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 120Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 66
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GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000685 AC XY: 51AN XY: 74500
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Macular corneal dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at