12-104757414-G-C

Position:

chr12-104757414-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018413.6(CHST11):c.670G>C(p.Ala224Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,613,938 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

CHST11
NM_018413.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.69

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007696897).

BP6

Variant 12-104757414-G-C is Benign according to our data. Variant chr12-104757414-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643254.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHST11	NM_018413.6 linkuse as main transcript	c.670G>C	p.Ala224Pro	missense_variant	3/3	ENST00000303694.6
CHST11	NM_001173982.2 linkuse as main transcript	c.655G>C	p.Ala219Pro	missense_variant	3/3
CHST11	XM_047428914.1 linkuse as main transcript	c.433G>C	p.Ala145Pro	missense_variant	2/2
CHST11	XM_047428915.1 linkuse as main transcript	c.433G>C	p.Ala145Pro	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST11	ENST00000303694.6 linkuse as main transcript	c.670G>C	p.Ala224Pro	missense_variant	3/3	1	NM_018413.6	P4	Q9NPF2-1
CHST11	ENST00000549260.5 linkuse as main transcript	c.655G>C	p.Ala219Pro	missense_variant	3/3	1		A1	Q9NPF2-2

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

411

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000750

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00435

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00261

AC:

656

AN:

251464

Hom.:

AF XY:

0.00255

AC XY:

347

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00439

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00381

AC:

5571

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

2659

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00440

Gnomad4 NFE exome

AF:

0.00449

Gnomad4 OTH exome

AF:

0.00328

GnomAD4 genome

AF:

0.00270

AC:

411

AN:

152046

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

190

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00435

Gnomad4 NFE

AF:

0.00413

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00266

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00255

AC:

310

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

CHST11: BS2 -

CHST11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 19, 2021

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

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-0.052

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.11

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.65

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.028

B;B

Vest4

0.25

MVP

0.70

MPC

1.1

ClinPred

0.022

GERP RS

5.4

Varity_R

0.37

gMVP

0.82

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