Genetic Variant CHST3:p.Gln330Lys (chr10-72008019-C-A) – 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_004273.5(CHST3):c.988C>A(p.Gln330Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHST3
NM_004273.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

Publications

1 publications found

Variant links:

Genes affected

CHST3 (HGNC:1971): (carbohydrate sulfotransferase 3) This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

CHST3 Gene-Disease associations (from GenCC):

spondyloepiphyseal dysplasia with congenital joint dislocations
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

CHST3 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=0.13100657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004273.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHST3	NM_004273.5	MANE Select	c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	NP_004264.2
CHST3	NM_001441201.1		c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	NP_001428130.1
CHST3	NM_001441202.1		c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	NP_001428131.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST3	ENST00000373115.5	TSL:1 MANE Select	c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	ENSP00000362207.4	Q7LGC8
CHST3	ENST00000879006.1		c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	ENSP00000549065.1
CHST3	ENST00000943244.1		c.988C>A	p.Gln330Lys	missense	Exon 3 of 3	ENSP00000613303.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1397202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689162

African (AFR)

AF:

0.00

AC:

AN:

31560

American (AMR)

AF:

0.00

AC:

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25140

East Asian (EAS)

AF:

0.00

AC:

AN:

35716

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078492

Other (OTH)

AF:

0.00

AC:

AN:

57932

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000184

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.12

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.55

M_CAP

Benign

0.053

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.34

PhyloP100

2.8

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.52

REVEL

Benign

0.18

Sift

Benign

0.39

Sift4G

Benign

0.76

Polyphen

0.27

Vest4

0.091

MutPred

0.41

Gain of ubiquitination at Q330 (P = 0.0185)

MVP

0.86

MPC

0.90

ClinPred

0.36

GERP RS

3.6

Varity_R

0.073

gMVP

0.45

Mutation Taster

=91/9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over