dbSNP rs267606732: 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, Labcorp Genetics (formerly Invitae), G2P

CHST3 links:

Genome browser will be placed here

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5 link	c.988C>A	p.Gln330Lys	missense_variant	Exon 3 of 3	ENST00000373115.5	NP_004264.2	Q7LGC8
CHST3	NM_001441201.1 link	c.988C>A	p.Gln330Lys	missense_variant	Exon 3 of 3		NP_001428130.1
CHST3	NM_001441202.1 link	c.988C>A	p.Gln330Lys	missense_variant	Exon 3 of 3		NP_001428131.1
CHST3	XM_011540369.3 link	c.988C>A	p.Gln330Lys	missense_variant	Exon 3 of 3		XP_011538671.1	Q7LGC8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5 link	c.988C>A	p.Gln330Lys	missense_variant	Exon 3 of 3	1	NM_004273.5	ENSP00000362207.4		Q7LGC8

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 v4.3

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

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over