12-104757040-G-A

Position:

chr12-104757040-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018413.6(CHST11):c.296G>A(p.Arg99Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R99W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

CHST11
NM_018413.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051530898).

BP6

Variant 12-104757040-G-A is Benign according to our data. Variant chr12-104757040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3051344.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHST11	NM_018413.6 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/3	ENST00000303694.6
CHST11	NM_001173982.2 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	3/3
CHST11	XM_047428914.1 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/2
CHST11	XM_047428915.1 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST11	ENST00000303694.6 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/3	1	NM_018413.6	P4	Q9NPF2-1
CHST11	ENST00000549260.5 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	3/3	1		A1	Q9NPF2-2
CHST11	ENST00000549016.1 linkuse as main transcript	c.176G>A	p.Arg59Gln	missense_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000419

AC:

105

AN:

250792

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000556

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000296

AC:

432

AN:

1461844

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

231

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000263

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000597

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHST11-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.81

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.88

T;T;T

Polyphen

0.93

P;P;.

Vest4

0.62

MVP

0.72

MPC

0.88

ClinPred

0.10

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.78

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