7-2433223-C-G

Variant names:

• chr7-2433223-C-G
• rs1782347611
• NM_018641.5:c.584C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018641.5(CHST12):​c.584C>G​(p.Pro195Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CHST12 NM_018641.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86
• Publications: 0 publications found

Genes affected

CHST12 (HGNC:17423): (carbohydrate sulfotransferase 12) 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 and desulfated dermatan sulfate. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. Alternatively spliced transcript variants differing only in their 5' UTRs have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018641.5. 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
	CHST12	NM_018641.5	MANE Select	c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	NP_061111.1	Q9NRB3
	CHST12	NM_001243794.2		c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	NP_001230723.1	Q9NRB3
	CHST12	NM_001243795.2		c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	NP_001230724.1	Q9NRB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST12	ENST00000618655.2	TSL:1 MANE Select	c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	ENSP00000481912.1	Q9NRB3
	CHST12	ENST00000258711.7	TSL:1	c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	ENSP00000258711.6	Q9NRB3
	CHST12	ENST00000852327.1		c.584C>G	p.Pro195Arg	missense	Exon 2 of 2	ENSP00000522386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459920 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726174

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111212

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.086	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.43
Sift	Benign	0.072	T
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.51		Gain of MoRF binding (P = 0.0016)
MVP		0.92
MPC		1.5
ClinPred		0.93	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.77
Mutation Taster		=39/61	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: rs1782347611; hg19: chr7-2472858;