NM_019886.4:c.70G>A

Variant names:

• chrX-46574001-G-A
• rs747186047
• NM_019886.4:c.70G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019886.4(CHST7):​c.70G>A​(p.Val24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 1,157,932 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 9.6e-7 (0 hom. 0 hem.)
• Consequence: CHST7 NM_019886.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.222
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15110049).

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.70G>A	p.Val24Met	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.70G>A	p.Val24Met	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
	CHST7	ENST00000868793.1		c.70G>A	p.Val24Met	missense	Exon 1 of 2	ENSP00000538852.1
	CHST7	ENST00000868794.1		c.70G>A	p.Val24Met	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111951 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

GnomAD2 exomes AF: 0.0000188 AC: 2 AN: 106256 AF XY: 0.0000272

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000235

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.56e-7 AC: 1 AN: 1045981 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 341941

African (AFR) AF: 0.00 AC: 0 AN: 25042

American (AMR) AF: 0.00 AC: 0 AN: 28605

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18633

East Asian (EAS) AF: 0.00 AC: 0 AN: 27416

South Asian (SAS) AF: 0.00 AC: 0 AN: 50010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3133

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 821520

Other (OTH) AF: 0.00 AC: 0 AN: 44438

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111951 Hom.: 0 Cov.: 24 AF XY: 0.0000292 AC XY: 1 AN XY: 34223

African (AFR) AF: 0.0000324 AC: 1 AN: 30832

American (AMR) AF: 0.00 AC: 0 AN: 10776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3523

South Asian (SAS) AF: 0.00 AC: 0 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6181

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52911

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.0000868 Hom.: 1

ExAC AF: 0.0000205 AC: 2

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	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.088	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.22
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.27
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.24		Loss of sheet (P = 0.0104)
MVP		0.88
ClinPred		0.028	T
GERP RS		0.32
PromoterAI		-0.062	Neutral
Varity_R		0.060
gMVP		0.62
Mutation Taster		=99/1	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: rs747186047; hg19: chrX-46433436;