12-104757403-A-G

Variant names:

• chr12-104757403-A-G
• rs1313972477
• NM_018413.6:c.659A>G

Variant summary

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

The NM_018413.6(CHST11):​c.659A>G​(p.Gln220Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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]

ACMG classification

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	c.659A>G	p.Gln220Arg	missense_variant	Exon 3 of 3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.644A>G	p.Gln215Arg	missense_variant	Exon 3 of 3		NP_001167453.1
CHST11	XM_047428914.1	c.422A>G	p.Gln141Arg	missense_variant	Exon 2 of 2		XP_047284870.1
CHST11	XM_047428915.1	c.422A>G	p.Gln141Arg	missense_variant	Exon 2 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.659A>G	p.Gln220Arg	missense_variant	Exon 3 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.644A>G	p.Gln215Arg	missense_variant	Exon 3 of 3	1		ENSP00000450004.1
CHST11	ENST00000549016.1	c.*64A>G		downstream_gene_variant		4		ENSP00000449095.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251464 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135918

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>G (p.Q220R) alteration is located in exon 3 (coding exon 3) of the CHST11 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the glutamine (Q) at amino acid position 220 to be replaced by an arginine (R). 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	Benign	0.14
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.89	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.34	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.49	P;P
Vest4		0.34
MutPred		0.83		.;Loss of helix (P = 0.1299);
MVP		0.82
MPC		0.97
ClinPred		0.48	T
GERP RS		5.4
Varity_R		0.15
gMVP		0.63

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

Other links and lift over

dbSNP: rs1313972477; hg19: chr12-105151181;