Variant 19-33689288-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001127895.2(CHST8):c.27G>A(p.Arg9Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,605,692 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0085 ( 82 hom. )

Consequence

CHST8
NM_001127895.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.55

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:

CHST8 (HGNC:):

CHST8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 19-33689288-G-A is Benign according to our data. Variant chr19-33689288-G-A is described in ClinVar as [Benign]. Clinvar id is 774526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.55 with no splicing effect.

BS2

High AC in GnomAd4 at 928 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST8	NM_001127895.2 linkuse as main transcript	c.27G>A	p.Arg9Arg	synonymous_variant	3/5	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.27G>A	p.Arg9Arg	synonymous_variant	3/5		NM_001127895.2	ENSP00000499084.1		Q9H2A9

Frequencies

GnomAD3 genomes

AF:

0.00610

AC:

928

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00882

Gnomad OTH

AF:

0.00960

GnomAD3 exomes

AF:

0.00744

AC:

1806

AN:

242674

Hom.:

AF XY:

0.00768

AC XY:

1009

AN XY:

131312

show subpopulations

Gnomad AFR exome

AF:

0.000819

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00554

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00956

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00852

AC:

12385

AN:

1453418

Hom.:

Cov.:

AF XY:

0.00849

AC XY:

6138

AN XY:

722944

show subpopulations

Gnomad4 AFR exome

AF:

0.00136

Gnomad4 AMR exome

AF:

0.00438

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00621

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00916

Gnomad4 OTH exome

AF:

0.00784

GnomAD4 genome

AF:

0.00609

AC:

928

AN:

152274

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00882

Gnomad4 OTH

AF:

0.00950

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.00547

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	CHST8: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.1

DANN

Benign

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