chr12-104757609-G-A

Position:

chr12-104757609-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018413.6(CHST11):c.865G>A(p.Val289Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,614,074 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

CHST11
NM_018413.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.46

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015352726).

BP6

Variant 12-104757609-G-A is Benign according to our data. Variant chr12-104757609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040663.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST11	NM_018413.6 linkuse as main transcript	c.865G>A	p.Val289Ile	missense_variant	3/3	ENST00000303694.6	NP_060883.1	Q9NPF2-1A0A024RBL0
CHST11	NM_001173982.2 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	3/3		NP_001167453.1	Q9NPF2-2
CHST11	XM_047428914.1 linkuse as main transcript	c.628G>A	p.Val210Ile	missense_variant	2/2		XP_047284870.1
CHST11	XM_047428915.1 linkuse as main transcript	c.628G>A	p.Val210Ile	missense_variant	2/2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6 linkuse as main transcript	c.865G>A	p.Val289Ile	missense_variant	3/3	1	NM_018413.6	ENSP00000305725.5		Q9NPF2-1
CHST11	ENST00000549260.5 linkuse as main transcript	c.850G>A	p.Val284Ile	missense_variant	3/3	1		ENSP00000450004.1		Q9NPF2-2

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00143

AC:

360

AN:

251438

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00132

AC:

1928

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1007

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.00515

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00124

AC:

189

AN:

152208

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000827

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00152

AC:

184

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHST11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 09, 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

0.059

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.22

.;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.074

Sift

Benign

0.27

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.011

B;B

Vest4

0.071

MVP

0.73

MPC

0.63

ClinPred

0.013

GERP RS

3.5

Varity_R

0.025

gMVP

0.46

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