X-46574068-C-T

Variant names:

• chrX-46574068-C-T
• rs770422083
• NM_019886.4:c.137C>T

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.137C>T​(p.Pro46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,405 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CHST7 NM_019886.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• Publications: 1 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=0.20618892).

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.137C>T	p.Pro46Leu	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.137C>T	p.Pro46Leu	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
	CHST7	ENST00000868793.1		c.137C>T	p.Pro46Leu	missense	Exon 1 of 2	ENSP00000538852.1
	CHST7	ENST00000868794.1		c.137C>T	p.Pro46Leu	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112405 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

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: 0.00000911 AC: 1 AN: 109735 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1053521 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 342963

African (AFR) AF: 0.00 AC: 0 AN: 25237

American (AMR) AF: 0.00 AC: 0 AN: 29003

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18629

East Asian (EAS) AF: 0.00 AC: 0 AN: 27762

South Asian (SAS) AF: 0.00 AC: 0 AN: 50255

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31921

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3259

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 822959

Other (OTH) AF: 0.00 AC: 0 AN: 44496

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112405 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34611

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000322 AC: 1 AN: 31014

American (AMR) AF: 0.00 AC: 0 AN: 10795

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3512

South Asian (SAS) AF: 0.00 AC: 0 AN: 2743

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6189

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53062

Other (OTH) AF: 0.00 AC: 0 AN: 1527

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.00000984 AC: 1

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	0.14
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	1.0	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	0.55	N
PhyloP100		1.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.36		Loss of loop (P = 0.0073)
MVP		0.82
ClinPred		0.035	T
GERP RS		0.64
PromoterAI		-0.0014	Neutral
Varity_R		0.094
gMVP		0.99
Mutation Taster		=95/5	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: rs770422083; hg19: chrX-46433503;