X-46574445-G-C

Variant names:

• chrX-46574445-G-C
• rs773697310
• NM_019886.4:c.514G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019886.4(CHST7):​c.514G>C​(p.Ala172Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 112,243 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic 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. A172T) 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: 0.660
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

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.514G>C	p.Ala172Pro	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.514G>C	p.Ala172Pro	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
	CHST7	ENST00000868793.1		c.514G>C	p.Ala172Pro	missense	Exon 1 of 2	ENSP00000538852.1
	CHST7	ENST00000868794.1		c.514G>C	p.Ala172Pro	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112243 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000324

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000891 AC: 1 AN: 112243 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34457

African (AFR) AF: 0.0000324 AC: 1 AN: 30877

American (AMR) AF: 0.00 AC: 0 AN: 10788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3506

South Asian (SAS) AF: 0.00 AC: 0 AN: 2757

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6121

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53124

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.0021	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.66
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.50
Sift	Benign	0.18	T
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.50
MutPred		0.47		Gain of glycosylation at A172 (P = 0.0164)
MVP		0.97
ClinPred		0.81	D
GERP RS		3.1
Varity_R		0.37
gMVP		0.98
Mutation Taster		=69/31	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

dbSNP: rs773697310; hg19: chrX-46433880;