Variant 12-104757268-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000303694.6(CHST11):c.524G>A(p.Arg175His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,614,066 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

CHST11
ENST00000303694.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHST11	NM_018413.6 linkuse as main transcript	c.524G>A	p.Arg175His	missense_variant	3/3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2 linkuse as main transcript	c.509G>A	p.Arg170His	missense_variant	3/3		NP_001167453.1
CHST11	XM_047428914.1 linkuse as main transcript	c.287G>A	p.Arg96His	missense_variant	2/2		XP_047284870.1
CHST11	XM_047428915.1 linkuse as main transcript	c.287G>A	p.Arg96His	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.524G>A	p.Arg175His	missense_variant	3/3	1	NM_018413.6	ENSP00000305725	P4	Q9NPF2-1
CHST11	ENST00000549260.5 linkuse as main transcript	c.509G>A	p.Arg170His	missense_variant	3/3	1		ENSP00000450004	A1	Q9NPF2-2
CHST11	ENST00000549016.1 linkuse as main transcript	c.404G>A	p.Arg135His	missense_variant	3/3	4		ENSP00000449095

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

251422

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

270

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

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

Aug 12, 2021

The c.524G>A (p.R175H) alteration is located in exon 3 (coding exon 3) of the CHST11 gene. This alteration results from a G to A substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 to be replaced by a histidine (H). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.74

.;D;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.4

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.89

MVP

0.96

MPC

1.9

ClinPred

0.41

GERP RS

5.4

Varity_R

0.55

gMVP

0.79

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