Genetic Variant NM_001127895.2:c.-87+3493C>T (chr19-33671336-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001127895.2(CHST8):c.-87+3493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,126 control chromosomes in the GnomAD database, including 1,568 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1568 hom., cov: 32)

Consequence

CHST8
NM_001127895.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST8	NM_001127895.2	MANE Select	c.-87+3493C>T		intron	N/A	NP_001121367.1	Q9H2A9
	CHST8	NM_001127896.2		c.-86-17840C>T		intron	N/A	NP_001121368.1	Q9H2A9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHST8	ENST00000650847.1	MANE Select	c.-87+3493C>T	intron	N/A	ENSP00000499084.1	Q9H2A9
CHST8	ENST00000438847.7	TSL:1	c.-86-17840C>T	intron	N/A	ENSP00000393879.1	Q9H2A9
CHST8	ENST00000434302.5	TSL:2	c.-87+3493C>T	intron	N/A	ENSP00000392604.1	Q9H2A9

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15581

AN:

152008

Hom.:

1551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.0663

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0836

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.103

AC:

15646

AN:

152126

Hom.:

1568

Cov.:

AF XY:

0.104

AC XY:

7756

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.252

AC:

10448

AN:

41472

American (AMR)

AF:

0.119

AC:

1818

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0513

AC:

178

AN:

3470

East Asian (EAS)

AF:

0.0665

AC:

343

AN:

5158

South Asian (SAS)

AF:

0.110

AC:

529

AN:

4820

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10594

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0264

AC:

1793

AN:

68008

Other (OTH)

AF:

0.0827

AC:

175

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

631

1262

1894

2525

3156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0515

Hom.:

155

Bravo

AF:

0.115

Asia WGS

AF:

0.109

AC:

380

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.012

(source)

DANN

Benign

0.58

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over