Genetic Variant CHST7:p.Ala172Thr (chrX-46574445-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_019886.4(CHST7):c.514G>A(p.Ala172Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,205,730 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 58 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 (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 5 hem., cov: 24)

Exomes 𝑓: 0.00014 ( 0 hom. 53 hem. )

Consequence

CHST7
NM_019886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.660

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3306003).

BS2

High Hemizygotes in GnomAd4 at 5 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.514G>A	p.Ala172Thr	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.514G>A	p.Ala172Thr	missense	Exon 1 of 2	ENSP00000276055.3	Q9NS84
CHST7	ENST00000868793.1		c.514G>A	p.Ala172Thr	missense	Exon 1 of 2	ENSP00000538852.1
CHST7	ENST00000868794.1		c.514G>A	p.Ala172Thr	missense	Exon 1 of 2	ENSP00000538853.1

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112243

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000757

AC:

AN:

171643

AF XY:

0.0000797

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.000139

AC:

152

AN:

1093487

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

360561

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26325

American (AMR)

AF:

0.0000285

AC:

AN:

35054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19286

East Asian (EAS)

AF:

0.00

AC:

AN:

30112

South Asian (SAS)

AF:

0.00

AC:

AN:

53958

European-Finnish (FIN)

AF:

0.0000262

AC:

AN:

38220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.000171

AC:

144

AN:

840505

Other (OTH)

AF:

0.000131

AC:

AN:

45911

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000116

AC:

AN:

112243

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34457

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30877

American (AMR)

AF:

0.0000927

AC:

AN:

10788

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3506

South Asian (SAS)

AF:

0.00

AC:

AN:

2757

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6121

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

53124

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.0000831

ExAC

AF:

0.0000752

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

0.077

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.37

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.1

PhyloP100

0.66

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.63

REVEL

Benign

0.18

Sift

Benign

0.99

Sift4G

Benign

0.67

Polyphen

0.97

Vest4

0.14

MVP

0.94

ClinPred

0.072

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.098

gMVP

0.88

Mutation Taster

=96/4

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

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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