X-46574889-G-A

Variant names:

• chrX-46574889-G-A
• rs61734023
• NM_019886.4:c.958G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019886.4(CHST7):​c.958G>A​(p.Val320Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000955 in 1,046,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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. V320L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.6e-7 (0 hom. 1 hem.)
• Consequence: CHST7 NM_019886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32390606).

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.958G>A	p.Val320Met	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.958G>A	p.Val320Met	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
	CHST7	ENST00000868793.1		c.958G>A	p.Val320Met	missense	Exon 1 of 2	ENSP00000538852.1
	CHST7	ENST00000868794.1		c.958G>A	p.Val320Met	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000105 AC: 1 AN: 95114 AF XY: 0.0000378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000531

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.55e-7 AC: 1 AN: 1046860 Hom.: 0 Cov.: 31 AF XY: 0.00000297 AC XY: 1 AN XY: 336396

African (AFR) AF: 0.00 AC: 0 AN: 24943

American (AMR) AF: 0.0000355 AC: 1 AN: 28161

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18066

East Asian (EAS) AF: 0.00 AC: 0 AN: 27492

South Asian (SAS) AF: 0.00 AC: 0 AN: 49010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3913

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819787

Other (OTH) AF: 0.00 AC: 0 AN: 44270

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.1	L
PhyloP100		0.55
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.30	N
REVEL	Uncertain	0.29
Sift	Benign	0.068	T
Sift4G	Benign	0.13	T
Polyphen		0.89	P
Vest4		0.13
MutPred		0.37		Gain of MoRF binding (P = 0.0875)
MVP		0.88
ClinPred		0.22	T
GERP RS		3.2
Varity_R		0.081
gMVP		0.37
Mutation Taster		=98/2	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: rs61734023; hg19: chrX-46434324; COSMIC: COSV52099809;