Variant chr19-33772230-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001127895.2(CHST8):c.442A>G(p.Ser148Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,597,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

CHST8
NM_001127895.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.229

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042159706).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST8	NM_001127895.2 linkuse as main transcript	c.442A>G	p.Ser148Gly	missense_variant	5/5	ENST00000650847.1	NP_001121367.1	Q9H2A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST8	ENST00000650847.1 linkuse as main transcript	c.442A>G	p.Ser148Gly	missense_variant	5/5		NM_001127895.2	ENSP00000499084.1		Q9H2A9

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

210388

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

117504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.000376

GnomAD4 exome

AF:

0.000334

AC:

483

AN:

1445268

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

224

AN XY:

718976

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000507

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:

0.000403

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000177

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.000242

AC:

ESP6500EA

AF:

0.000247

AC:

ExAC

AF:

0.000238

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.442A>G (p.S148G) alteration is located in exon 4 (coding exon 3) of the CHST8 gene. This alteration results from a A to G substitution at nucleotide position 442, causing the serine (S) at amino acid position 148 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.3

DANN

Benign

0.87

DEOGEN2

Benign

0.13

.;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.42

T;T;.;.

M_CAP

Benign

0.064

MetaRNN

Benign

0.042

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

.;L;L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

.;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.15

.;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.13, 0.13, 0.13

MVP

0.72

MPC

0.51

ClinPred

0.015

GERP RS

-10

Varity_R

0.057

gMVP

0.46

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