16-75479743-G-A

Position:

• chr16-75479743-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021615.5(CHST6):​c.86C>T​(p.Pro29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CHST6 NM_021615.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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]

ENSG00000203472 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21940133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST6	NM_021615.5	c.86C>T	p.Pro29Leu	missense_variant	3/3	ENST00000332272.9	NP_067628.1
CHST6	NR_163480.1	n.733+2074C>T		intron_variant
CHST6	NR_163481.1	n.577+2074C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST6	ENST00000332272.9	c.86C>T	p.Pro29Leu	missense_variant	3/3	3	NM_021615.5	ENSP00000328983.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452156 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 721612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Macular corneal dystrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Apr 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.31	T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.78	.;.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Uncertain	-0.067	T
MutationAssessor	Benign	1.9	M;M;M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N;.;N
REVEL	Benign	0.27
Sift	Benign	0.65	T;.;T
Sift4G	Benign	0.70	T;.;T
Polyphen		0.88	P;P;P
Vest4		0.052
MutPred		0.40		Loss of glycosylation at P29 (P = 0.0205);Loss of glycosylation at P29 (P = 0.0205);Loss of glycosylation at P29 (P = 0.0205);
MVP		0.90
MPC		0.44
ClinPred		0.15	T
GERP RS		1.5
Varity_R		0.020
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1443299574; hg19: chr16-75513641;