chr12-104457440-G-T

Variant names:

• chr12-104457440-G-T
• rs374980790
• NM_018413.6:c.29G>T

Variant summary

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

The NM_018413.6(CHST11):​c.29G>T​(p.Arg10Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,372 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.66

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.29G>T	p.Arg10Met	missense_variant	Exon 1 of 3	ENST00000303694.6	NP_060883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.29G>T	p.Arg10Met	missense_variant	Exon 1 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.29G>T	p.Arg10Met	missense_variant	Exon 1 of 3	1		ENSP00000450004.1
CHST11	ENST00000547956.1	c.29G>T	p.Arg10Met	missense_variant	Exon 1 of 2	2		ENSP00000449093.1
CHST11	ENST00000546689.1	c.29G>T	p.Arg10Met	missense_variant	Exon 1 of 2	2		ENSP00000448678.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74516

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;.;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Uncertain	-0.073	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.8	D;N;N;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0, 0.97	.;D;D;.
Vest4		0.80
MutPred		0.34		Loss of MoRF binding (P = 0.0516);Loss of MoRF binding (P = 0.0516);Loss of MoRF binding (P = 0.0516);Loss of MoRF binding (P = 0.0516);
MVP		0.94
MPC		1.7
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.7
Varity_R		0.35
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: rs374980790; hg19: chr12-104851218;