16-75478836-C-A

Position:

chr16-75478836-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_021615.5(CHST6):c.993G>T(p.Gln331His) variant causes a missense change. The variant allele was found at a frequency of 0.00232 in 1,613,470 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 63 hom. )

Consequence

CHST6
NM_021615.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 4.82

Variant links:

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 links:

ENSG00000203472 (HGNC:):

ENSG00000203472 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011656791).

BP6

Variant 16-75478836-C-A is Benign according to our data. Variant chr16-75478836-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196507.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}. Variant chr16-75478836-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00163 (249/152370) while in subpopulation SAS AF= 0.0213 (103/4828). AF 95% confidence interval is 0.018. There are 2 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST6	NM_021615.5 linkuse as main transcript	c.993G>T	p.Gln331His	missense_variant	3/3	ENST00000332272.9	NP_067628.1	Q9GZX3
CHST6	NR_163480.1 linkuse as main transcript	n.733+2981G>T		intron_variant
CHST6	NR_163481.1 linkuse as main transcript	n.577+2981G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST6	ENST00000332272.9 linkuse as main transcript	c.993G>T	p.Gln331His	missense_variant	3/3	3	NM_021615.5	ENSP00000328983.4		Q9GZX3

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00404

AC:

1014

AN:

250718

Hom.:

AF XY:

0.00530

AC XY:

719

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0250

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000857

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00239

AC:

3495

AN:

1461100

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2344

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0261

Gnomad4 FIN exome

AF:

0.0000759

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00163

AC:

249

AN:

152370

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00414

AC:

503

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00136

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Macular corneal dystrophy

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

D;D;D

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;.;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.1

D;.;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0020

D;.;D

Sift4G

Benign

0.087

T;.;T

Polyphen

1.0

D;D;D

Vest4

0.51

MutPred

0.48

Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);

MVP

1.0

MPC

0.88

ClinPred

0.027

GERP RS

4.9

Varity_R

0.63

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over