12-104457440-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018413.6(CHST11):​c.29G>C​(p.Arg10Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.66
• Publications: 1 publications found

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]

CHST11 Gene-Disease associations (from GenCC):

• osteochondrodysplasia, brachydactyly, and overlapping malformed digits

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018413.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST11	NM_018413.6	MANE Select	c.29G>C	p.Arg10Thr	missense	Exon 1 of 3	NP_060883.1	Q9NPF2-1
	CHST11	NM_001173982.2		c.29G>C	p.Arg10Thr	missense	Exon 1 of 3	NP_001167453.1	Q9NPF2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST11	ENST00000303694.6	TSL:1 MANE Select	c.29G>C	p.Arg10Thr	missense	Exon 1 of 3	ENSP00000305725.5	Q9NPF2-1
	CHST11	ENST00000549260.5	TSL:1	c.29G>C	p.Arg10Thr	missense	Exon 1 of 3	ENSP00000450004.1	Q9NPF2-2
	CHST11	ENST00000547956.1	TSL:2	c.29G>C	p.Arg10Thr	missense	Exon 1 of 2	ENSP00000449093.1	F8VXK7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251322 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111900

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.43		Loss of MoRF binding (P = 0.0361)
MVP		0.94
MPC		1.8
ClinPred		0.99	D
GERP RS		5.2
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.7
Varity_R		0.50
gMVP		0.66
Mutation Taster		=10/90	disease causing

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

Other links and lift over

dbSNP: rs374980790; hg19: chr12-104851218;