Genetic Variant NM_019886.4:c.70G>C (chrX-46574001-G-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.70G>C(p.Val24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,157,932 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V24M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00013 ( 0 hom. 38 hem. )

Consequence

CHST7
NM_019886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.222

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:

Genome browser will be placed here

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=0.16489902).

BS2

High Hemizygotes in GnomAd4 at 4 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.70G>C	p.Val24Leu	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.70G>C	p.Val24Leu	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
CHST7	ENST00000868793.1		c.70G>C	p.Val24Leu	missense	Exon 1 of 2	ENSP00000538852.1
CHST7	ENST00000868794.1		c.70G>C	p.Val24Leu	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes

AF:

0.0000983

AC:

AN:

111951

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:

0.000324

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000565

AC:

AN:

106256

AF XY:

0.0000272

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:

0.000402

Gnomad NFE exome

AF:

0.0000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

137

AN:

1045981

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

341941

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25042

American (AMR)

AF:

0.00

AC:

AN:

28605

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18633

East Asian (EAS)

AF:

0.00

AC:

AN:

27416

South Asian (SAS)

AF:

0.00

AC:

AN:

50010

European-Finnish (FIN)

AF:

0.000368

AC:

AN:

27184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3133

European-Non Finnish (NFE)

AF:

0.000153

AC:

126

AN:

821520

Other (OTH)

AF:

0.0000225

AC:

AN:

44438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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:

0.0000983

AC:

AN:

111951

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34223

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30832

American (AMR)

AF:

0.00

AC:

AN:

10776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2669

European-Finnish (FIN)

AF:

0.000324

AC:

AN:

6181

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000170

AC:

AN:

52911

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.00

Hom.:

Bravo

AF:

0.0000491

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

0.064

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.076

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.55

PhyloP100

-0.22

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.31

REVEL

Uncertain

0.31

Sift

Benign

0.65

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.14

MutPred

0.26

Loss of sheet (P = 0.0063)

MVP

0.88

ClinPred

0.015

GERP RS

0.32

PromoterAI

0.039

Neutral

(source)

Varity_R

0.074

gMVP

0.67

Mutation Taster

=99/1

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