Genetic Variant CHST7:p.Val28Ala (chrX-46574014-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019886.4(CHST7):c.83T>C(p.Val28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,158,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 13 hem. )

Consequence

CHST7
NM_019886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668

Publications

0 publications found

Variant links:

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]

CHST7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2187644).

BS2

High Hemizygotes in GnomAd4 at 3 gene

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.83T>C	p.Val28Ala	missense	Exon 1 of 2	NP_063939.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST7	ENST00000276055.4	TSL:1 MANE Select	c.83T>C	p.Val28Ala	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
CHST7	ENST00000868793.1		c.83T>C	p.Val28Ala	missense	Exon 1 of 2	ENSP00000538852.1
CHST7	ENST00000868794.1		c.83T>C	p.Val28Ala	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000332

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000759

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

106846

AF XY:

0.0000273

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000700

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1047117

Hom.:

Cov.:

AF XY:

0.0000380

AC XY:

AN XY:

342057

show subpopulations

African (AFR)

AF:

0.0000798

AC:

AN:

25077

American (AMR)

AF:

0.00

AC:

AN:

28786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18634

East Asian (EAS)

AF:

0.00

AC:

AN:

27468

South Asian (SAS)

AF:

0.00

AC:

AN:

50077

European-Finnish (FIN)

AF:

0.000291

AC:

AN:

27512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3145

European-Non Finnish (NFE)

AF:

0.0000511

AC:

AN:

821978

Other (OTH)

AF:

0.0000225

AC:

AN:

44440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111064

Hom.:

Cov.:

AF XY:

0.0000896

AC XY:

AN XY:

33472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30472

American (AMR)

AF:

0.00

AC:

AN:

10717

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2635

East Asian (EAS)

AF:

0.00

AC:

AN:

3473

South Asian (SAS)

AF:

0.00

AC:

AN:

2612

European-Finnish (FIN)

AF:

0.000332

AC:

AN:

6030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000759

AC:

AN:

52715

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000612

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000102

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.091

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

0.0

PhyloP100

0.67

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.61

REVEL

Benign

0.27

Sift

Uncertain

0.0040

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.073

MutPred

0.32

Loss of sheet (P = 0.0104)

MVP

0.90

ClinPred

0.066

GERP RS

3.6

PromoterAI

-0.057

Neutral

(source)

Varity_R

0.12

gMVP

0.83

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over