X-46574487-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1 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

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 Likely_benign. Variant got -2 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CHST7_HUMAN
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST7	NM_019886.4	c.556A>G	p.Asn186Asp	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.556A>G	p.Asn186Asp	missense_variant	Exon 1 of 2	1	NM_019886.4	ENSP00000276055.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000595

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.556A>G (p.N186D) alteration is located in exon 1 (coding exon 1) of the CHST7 gene. This alteration results from a A to G substitution at nucleotide position 556, causing the asparagine (N) at amino acid position 186 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-46433922;