chrX-46574487-A-G

Variant names:

• chrX-46574487-A-G
• NM_019886.4:c.556A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_019886.4(CHST7):​c.556A>G​(p.Asn186Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000457 in 1,093,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: CHST7 NM_019886.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.34
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019886.4. 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
	CHST7	NM_019886.4	MANE Select	c.556A>G	p.Asn186Asp	missense	Exon 1 of 2	NP_063939.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST7	ENST00000276055.4	TSL:1 MANE Select	c.556A>G	p.Asn186Asp	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
	CHST7	ENST00000868793.1		c.556A>G	p.Asn186Asp	missense	Exon 1 of 2	ENSP00000538852.1
	CHST7	ENST00000868794.1		c.556A>G	p.Asn186Asp	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1093350 Hom.: 0 Cov.: 32 AF XY: 0.00000555 AC XY: 2 AN XY: 360096

African (AFR) AF: 0.00 AC: 0 AN: 26314

American (AMR) AF: 0.00 AC: 0 AN: 34914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19246

East Asian (EAS) AF: 0.00 AC: 0 AN: 30087

South Asian (SAS) AF: 0.00 AC: 0 AN: 53676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39363

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4111

European-Non Finnish (NFE) AF: 0.00000595 AC: 5 AN: 839794

Other (OTH) AF: 0.00 AC: 0 AN: 45845

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.9	L
PhyloP100		5.3
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.36		Loss of MoRF binding (P = 0.0645)
MVP		0.92
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.51
gMVP		1.0
Mutation Taster		=53/47	polymorphism

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

hg19: chrX-46433922;