chr12-104457433-G-A

Position:

• chr12-104457433-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018413.6(CHST11):​c.22G>A​(p.Val8Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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: 6.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2145823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST11	NM_018413.6	c.22G>A	p.Val8Met	missense_variant	1/3	ENST00000303694.6
CHST11	NM_001173982.2	c.22G>A	p.Val8Met	missense_variant	1/3
CHST11	XM_047428914.1	c.-130G>A		5_prime_UTR_variant	1/2
CHST11	XM_047428915.1	c.-115G>A		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST11	ENST00000303694.6	c.22G>A	p.Val8Met	missense_variant	1/3	1	NM_018413.6	P4
CHST11	ENST00000549260.5	c.22G>A	p.Val8Met	missense_variant	1/3	1		A1
CHST11	ENST00000547956.1	c.22G>A	p.Val8Met	missense_variant	1/2	2
CHST11	ENST00000546689.1	c.22G>A	p.Val8Met	missense_variant	1/2	2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.22G>A (p.V8M) alteration is located in exon 1 (coding exon 1) of the CHST11 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the valine (V) at amino acid position 8 to be replaced by a methionine (M). 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	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	T;.;T;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.0	.;N;N;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.43	N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Benign	0.066	T;T;T;D
Polyphen		0.021, 0.46	.;B;P;.
Vest4		0.43
MutPred		0.21		Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);
MVP		0.68
MPC		0.67
ClinPred		0.68	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.46

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: chr12-104851211;