Variant 12-104457415-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000303694.6(CHST11):c.4A>C(p.Lys2Gln) 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
ENST00000303694.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.14

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/exons	MANE	Protein
CHST11	NM_018413.6 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/3		NP_001167453.1
CHST11	XM_047428914.1 linkuse as main transcript	c.-148A>C		5_prime_UTR_variant	1/2		XP_047284870.1
CHST11	XM_047428915.1 linkuse as main transcript	c.-133A>C		5_prime_UTR_variant	1/2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/3	1	NM_018413.6	ENSP00000305725	P4	Q9NPF2-1
CHST11	ENST00000549260.5 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/3	1		ENSP00000450004	A1	Q9NPF2-2
CHST11	ENST00000547956.1 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/2	2		ENSP00000449093
CHST11	ENST00000546689.1 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/2	2		ENSP00000448678

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.4A>C (p.K2Q) alteration is located in exon 1 (coding exon 1) of the CHST11 gene. This alteration results from a A to C substitution at nucleotide position 4, causing the lysine (K) at amino acid position 2 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

T;T;T;T

M_CAP

Uncertain

0.086

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.2

.;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.97, 0.95

.;D;P;.

Vest4

0.51

MutPred

0.15

Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);

MVP

0.69

MPC

1.0

ClinPred

0.96

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over