chr19-33670416-T-C

Variant names:

• chr19-33670416-T-C
• rs10500266
• NM_001127895.2:c.-87+2573T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127895.2(CHST8):​c.-87+2573T>C 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 152,212 control chromosomes in the GnomAD database, including 1,571 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 (1571 hom., cov: 33)
• Consequence: CHST8 NM_001127895.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 2 publications found

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: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST8	NM_001127895.2	c.-87+2573T>C		intron_variant	Intron 2 of 4	ENST00000650847.1	NP_001121367.1
CHST8	NM_001127896.2	c.-86-18760T>C		intron_variant	Intron 1 of 3		NP_001121368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST8	ENST00000650847.1	c.-87+2573T>C		intron_variant	Intron 2 of 4		NM_001127895.2	ENSP00000499084.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15630 AN: 152094 Hom.: 1554 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0265

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: 15695 AN: 152212 Hom.: 1571 Cov.: 33 AF XY: 0.105 AC XY: 7778 AN XY: 74426

African (AFR) AF: 0.252 AC: 10449 AN: 41506

American (AMR) AF: 0.119 AC: 1823 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.0670 AC: 347 AN: 5180

South Asian (SAS) AF: 0.110 AC: 530 AN: 4814

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10606

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0265 AC: 1803 AN: 68020

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.0644 Hom.: 311

Bravo AF: 0.116

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.67
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10500266; hg19: chr19-34161322;