rs17325700

Variant names:

• chr19-33740922-A-T
• rs17325700
• NM_001127895.2:c.131-30491A>T

Variant summary

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

The NM_001127895.2(CHST8):​c.131-30491A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,166 control chromosomes in the GnomAD database, including 648 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 0.086 (648 hom., cov: 32)
• Consequence: CHST8 NM_001127895.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST8	NM_001127895.2	MANE Select	c.131-30491A>T		intron	N/A	NP_001121367.1
	CHST8	NM_001127896.2		c.131-30491A>T		intron	N/A	NP_001121368.1
	CHST8	NM_022467.3		c.131-30491A>T		intron	N/A	NP_071912.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST8	ENST00000650847.1	MANE Select	c.131-30491A>T		intron	N/A	ENSP00000499084.1
	CHST8	ENST00000262622.4	TSL:1	c.131-30491A>T		intron	N/A	ENSP00000262622.3
	CHST8	ENST00000438847.7	TSL:1	c.131-30491A>T		intron	N/A	ENSP00000393879.1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13046 AN: 152048 Hom.: 642 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0859 AC: 13077 AN: 152166 Hom.: 648 Cov.: 32 AF XY: 0.0886 AC XY: 6587 AN XY: 74374

African (AFR) AF: 0.0386 AC: 1603 AN: 41524

American (AMR) AF: 0.111 AC: 1701 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.0325 AC: 168 AN: 5176

South Asian (SAS) AF: 0.0970 AC: 467 AN: 4816

European-Finnish (FIN) AF: 0.140 AC: 1484 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6766 AN: 67986

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0908 Hom.: 79

Bravo AF: 0.0829

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.42
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: rs17325700; hg19: chr19-34231827;