chr19-33772017-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001127895.2(CHST8):c.229C>T(p.Arg77Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,609,794 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R77R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 31 hom. )

Consequence

CHST8
NM_001127895.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 0.253

Publications

12 publications found

Variant links:

Genes affected

CHST8 (HGNC:15993): (carbohydrate sulfotransferase 8) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is predominantly expressed in the pituitary gland, and is localized to the golgi membrane. This protein catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. It is responsible for sulfation of GalNAc on luteinizing hormone (LH), which is required for production of the sex hormones. Mice lacking this enzyme, exhibit increased levels of circulating LH, and precocious sexual maturation of both male and female mice. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

CHST8 Gene-Disease associations (from GenCC):

peeling skin syndrome type A
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

CHST8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013044834).

BP6

Variant 19-33772017-C-T is Benign according to our data. Variant chr19-33772017-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 183645.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127895.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST8	NM_001127895.2	MANE Select	c.229C>T	p.Arg77Trp	missense	Exon 5 of 5	NP_001121367.1	Q9H2A9
CHST8	NM_001127896.2		c.229C>T	p.Arg77Trp	missense	Exon 4 of 4	NP_001121368.1	Q9H2A9
CHST8	NM_022467.3		c.229C>T	p.Arg77Trp	missense	Exon 4 of 4	NP_071912.2	Q9H2A9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST8	ENST00000650847.1	MANE Select	c.229C>T	p.Arg77Trp	missense	Exon 5 of 5	ENSP00000499084.1	Q9H2A9
CHST8	ENST00000262622.4	TSL:1	c.229C>T	p.Arg77Trp	missense	Exon 4 of 4	ENSP00000262622.3	Q9H2A9
CHST8	ENST00000438847.7	TSL:1	c.229C>T	p.Arg77Trp	missense	Exon 4 of 4	ENSP00000393879.1	Q9H2A9

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

535

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00569

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00399

AC:

976

AN:

244402

AF XY:

0.00428

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00299

Gnomad NFE exome

AF:

0.00593

Gnomad OTH exome

AF:

0.00320

GnomAD4 exome

AF:

0.00593

AC:

8638

AN:

1457476

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

4225

AN XY:

724898

show subpopulations

African (AFR)

AF:

0.000931

AC:

AN:

33314

American (AMR)

AF:

0.00237

AC:

104

AN:

43912

Ashkenazi Jewish (ASJ)

AF:

0.000116

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00536

AC:

460

AN:

85888

European-Finnish (FIN)

AF:

0.00293

AC:

153

AN:

52284

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00680

AC:

7552

AN:

1110596

Other (OTH)

AF:

0.00545

AC:

328

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

514

1029

1543

2058

2572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00351

AC:

535

AN:

152318

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41582

American (AMR)

AF:

0.00411

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00290

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00569

AC:

387

AN:

68020

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00376

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00420

AC:

510

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00687

EpiControl

AF:

0.00587

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Peeling skin syndrome type A (2)

CHST8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.81

PhyloP100

0.25

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.40

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

0.95

Vest4

0.72

MVP

0.96

MPC

0.93

ClinPred

0.022

GERP RS

4.0

Varity_R

0.070

gMVP

0.45

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over