Genetic Variant CHSY3:p.Gln60Leu (chr5-129905008-A-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_175856.5(CHSY3):c.179A>T(p.Gln60Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHSY3
NM_175856.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.871

Publications

0 publications found

Variant links:

Genes affected

CHSY3 (HGNC:24293): (chondroitin sulfate synthase 3) CSS3 is a glycosyltransferase that has both glucuronyltransferase and N-acetylgalactosaminyltransferase activities (Yada et al., 2003 [PubMed 12907687]).[supplied by OMIM, Mar 2008]

CHSY3 links:

ENSG00000251680 (HGNC:58253):

ENSG00000251680 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=0.13778195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY3	NM_175856.5 link	c.179A>T	p.Gln60Leu	missense_variant	Exon 1 of 3	ENST00000305031.5	NP_787052.3	Q70JA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY3	ENST00000305031.5 link	c.179A>T	p.Gln60Leu	missense_variant	Exon 1 of 3	1	NM_175856.5	ENSP00000302629.4		Q70JA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

168838

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699728

African (AFR)

AF:

0.00

AC:

AN:

32166

American (AMR)

AF:

0.00

AC:

AN:

41172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25394

East Asian (EAS)

AF:

0.00

AC:

AN:

37452

South Asian (SAS)

AF:

0.00

AC:

AN:

81316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093868

Other (OTH)

AF:

0.00

AC:

AN:

58696

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000893

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.179A>T (p.Q60L) alteration is located in exon 1 (coding exon 1) of the CHSY3 gene. This alteration results from a A to T substitution at nucleotide position 179, causing the glutamine (Q) at amino acid position 60 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.87

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.46

REVEL

Benign

0.059

Sift

Benign

0.093

Sift4G

Benign

0.35

Polyphen

0.12

Vest4

0.24

MutPred

0.26

Loss of solvent accessibility (P = 0.0056);

MVP

0.61

MPC

1.6

ClinPred

0.11

GERP RS

3.0

Varity_R

0.11

gMVP

0.56

Mutation Taster

=88/12

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over