X-46574476-C-T

Variant names:

• chrX-46574476-C-T
• rs752917425
• NM_019886.4:c.545C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019886.4(CHST7):​c.545C>T​(p.Pro182Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000888 in 112,588 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P182R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
• Consequence: CHST7 NM_019886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20

Genes affected

CHST7 (HGNC:13817): (carbohydrate sulfotransferase 7) This gene is a member of the Gal/GalNAc/GlcNAc (galactose/N-acetylgalactosamine/N-acetylglucosamine) 6-O-sulfotransferase (GST) family. Members of this family encode enzymes that catalyze the specific addition of sulfate groups to distinct hydroxyl and amino groups of carbohydrates. The encoded protein catalyzes the sulfation of 6-hydroxyl group of GalNAc in chondroitin. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4223267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST7	NM_019886.4	c.545C>T	p.Pro182Leu	missense_variant	Exon 1 of 2	ENST00000276055.4	NP_063939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST7	ENST00000276055.4	c.545C>T	p.Pro182Leu	missense_variant	Exon 1 of 2	1	NM_019886.4	ENSP00000276055.3

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112588 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34792

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112588 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34792

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000540 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.11	T
Polyphen		0.85	P
Vest4		0.20
MutPred		0.44		Gain of helix (P = 0.0034);
MVP		0.90
ClinPred		0.85	D
GERP RS		4.0
Varity_R		0.32
gMVP		0.80

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

Other links and lift over

dbSNP: rs752917425; hg19: chrX-46433911;