Variant 12-104757403-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018413.6(CHST11):c.659A>G(p.Gln220Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CHST11
NM_018413.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

CHST11 (HGNC:17422): (carbohydrate sulfotransferase 11) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. A chromosomal translocation involving this gene and IgH, t(12;14)(q23;q32), has been reported in a patient with B-cell chronic lymphocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CHST11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6 link	c.659A>G	p.Gln220Arg	missense_variant	Exon 3 of 3	ENST00000303694.6	NP_060883.1	Q9NPF2-1A0A024RBL0
CHST11	NM_001173982.2 link	c.644A>G	p.Gln215Arg	missense_variant	Exon 3 of 3		NP_001167453.1	Q9NPF2-2
CHST11	XM_047428914.1 link	c.422A>G	p.Gln141Arg	missense_variant	Exon 2 of 2		XP_047284870.1
CHST11	XM_047428915.1 link	c.422A>G	p.Gln141Arg	missense_variant	Exon 2 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6 link	c.659A>G	p.Gln220Arg	missense_variant	Exon 3 of 3	1	NM_018413.6	ENSP00000305725.5		Q9NPF2-1
CHST11	ENST00000549260.5 link	c.644A>G	p.Gln215Arg	missense_variant	Exon 3 of 3	1		ENSP00000450004.1		Q9NPF2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251464

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>G (p.Q220R) alteration is located in exon 3 (coding exon 3) of the CHST11 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the glutamine (Q) at amino acid position 220 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.89

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.34

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.49

P;P

Vest4

0.34

MutPred

0.83

.;Loss of helix (P = 0.1299);

MVP

0.82

MPC

0.97

ClinPred

0.48

GERP RS

5.4

Varity_R

0.15

gMVP

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over