12-104457415-A-C

Variant names:

• chr12-104457415-A-C
• NM_018413.6:c.4A>C

Variant summary

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

The NM_018413.6(CHST11):​c.4A>C​(p.Lys2Gln) 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: 8.14

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.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 3		NP_001167453.1
CHST11	XM_047428914.1	c.-148A>C		5_prime_UTR_variant	Exon 1 of 2		XP_047284870.1
CHST11	XM_047428915.1	c.-133A>C		5_prime_UTR_variant	Exon 1 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 3	1		ENSP00000450004.1
CHST11	ENST00000547956.1	c.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 2	2		ENSP00000449093.1
CHST11	ENST00000546689.1	c.4A>C	p.Lys2Gln	missense_variant	Exon 1 of 2	2		ENSP00000448678.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4A>C (p.K2Q) alteration is located in exon 1 (coding exon 1) of the CHST11 gene. This alteration results from a A to C substitution at nucleotide position 4, causing the lysine (K) at amino acid position 2 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.2	.;L;L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.97, 0.95	.;D;P;.
Vest4		0.51
MutPred		0.15		Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);Loss of ubiquitination at K2 (P = 0.0116);
MVP		0.69
MPC		1.0
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-104851193;