Genetic Variant CHST15:p.Ala283Thr (chr10-124044619-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001270764.2(CHST15):c.847G>A(p.Ala283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000038 in 1,577,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A283S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CHST15
NM_001270764.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.55

Publications

0 publications found

Variant links:

Genes affected

CHST15 (HGNC:18137): (carbohydrate sulfotransferase 15) Chondroitin sulfate (CS) is a glycosaminoglycan which is an important structural component of the extracellular matrix and which links to proteins to form proteoglycans. Chondroitin sulfate E (CS-E) is an isomer of chondroitin sulfate in which the C-4 and C-6 hydroxyl groups are sulfated. This gene encodes a type II transmembrane glycoprotein that acts as a sulfotransferase to transfer sulfate to the C-6 hydroxal group of chondroitin sulfate. This gene has also been identified as being co-expressed with RAG1 in B-cells and as potentially acting as a B-cell surface signaling receptor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

CHST15 links:

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ACMG classification

Classification was made for transcript

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=0.15237534).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270764.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST15	NM_001270764.2	MANE Select	c.847G>A	p.Ala283Thr	missense	Exon 3 of 8	NP_001257693.1	Q7LFX5-1
CHST15	NM_015892.5		c.847G>A	p.Ala283Thr	missense	Exon 3 of 8	NP_056976.2
CHST15	NM_001270765.2		c.847G>A	p.Ala283Thr	missense	Exon 3 of 6	NP_001257694.1	Q7LFX5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST15	ENST00000435907.6	TSL:1 MANE Select	c.847G>A	p.Ala283Thr	missense	Exon 3 of 8	ENSP00000402394.1	Q7LFX5-1
CHST15	ENST00000346248.7	TSL:1	c.847G>A	p.Ala283Thr	missense	Exon 3 of 8	ENSP00000333947.6	Q7LFX5-1
CHST15	ENST00000874549.1		c.847G>A	p.Ala283Thr	missense	Exon 3 of 8	ENSP00000544608.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

223892

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1425414

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31696

American (AMR)

AF:

0.00

AC:

AN:

39912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24622

East Asian (EAS)

AF:

0.00

AC:

AN:

37520

South Asian (SAS)

AF:

0.00

AC:

AN:

82904

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00000366

AC:

AN:

1091822

Other (OTH)

AF:

0.00

AC:

AN:

58706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.017

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0051

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

4.6

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.050

REVEL

Benign

0.10

Sift

Benign

0.40

Sift4G

Benign

0.71

Polyphen

0.29

Vest4

0.24

MutPred

0.41

Gain of loop (P = 0.0312)

MVP

0.53

MPC

0.30

ClinPred

0.82

GERP RS

5.7

Varity_R

0.16

gMVP

0.75

Mutation Taster

=81/19

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