12-104757187-T-G

Position:

• chr12-104757187-T-G

Variant summary

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

The NM_018413.6(CHST11):​c.443T>G​(p.Met148Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 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: 0.0000041 (0 hom.)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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/exons	MANE	Protein	UniProt
CHST11	NM_018413.6	c.443T>G	p.Met148Arg	missense_variant	3/3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.428T>G	p.Met143Arg	missense_variant	3/3		NP_001167453.1
CHST11	XM_047428914.1	c.206T>G	p.Met69Arg	missense_variant	2/2		XP_047284870.1
CHST11	XM_047428915.1	c.206T>G	p.Met69Arg	missense_variant	2/2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.443T>G	p.Met148Arg	missense_variant	3/3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.428T>G	p.Met143Arg	missense_variant	3/3	1		ENSP00000450004.1
CHST11	ENST00000549016.1	c.323T>G	p.Met108Arg	missense_variant	3/3	4		ENSP00000449095.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.443T>G (p.M148R) alteration is located in exon 3 (coding exon 3) of the CHST11 gene. This alteration results from a T to G substitution at nucleotide position 443, causing the methionine (M) at amino acid position 148 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	0.25
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.28	.;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.089
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.77	.;N;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.76
MutPred		0.50		.;Gain of solvent accessibility (P = 0.0044);.;
MVP		0.70
MPC		1.0
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.66
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-105150965;