Genetic Variant NM_018413.6:c.124C>G (chr12-104601911-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018413.6(CHST11):c.124C>G(p.Arg42Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHST11
NM_018413.6 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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 rank	MANE	Protein	UniProt
CHST11	NM_018413.6 link	c.124C>G	p.Arg42Gly	missense_variant	Exon 2 of 3	ENST00000303694.6	NP_060883.1	Q9NPF2-1A0A024RBL0
CHST11	NM_001173982.2 link	c.109C>G	p.Arg37Gly	missense_variant	Exon 2 of 3		NP_001167453.1	Q9NPF2-2
CHST11	XM_047428914.1 link	c.-34+144382C>G		intron_variant	Intron 1 of 1		XP_047284870.1
CHST11	XM_047428915.1 link	c.-34+144397C>G		intron_variant	Intron 1 of 1		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6 link	c.124C>G	p.Arg42Gly	missense_variant	Exon 2 of 3	1	NM_018413.6	ENSP00000305725.5		Q9NPF2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;T;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.95

.;.;L;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.010

D;T;T;D;D

Sift4G

Benign

0.086

T;T;T;D;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.60

MutPred

0.68

Loss of helix (P = 0.0196);.;Loss of helix (P = 0.0196);.;.;

MVP

0.77

MPC

0.88

ClinPred

0.54

GERP RS

4.8

Varity_R

0.15

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over