7-2432800-C-G

Variant names:

• chr7-2432800-C-G
• rs563115579
• NM_018641.5:c.161C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018641.5(CHST12):​c.161C>G​(p.Pro54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. P54L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHST12 NM_018641.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07097867).

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.161C>G	p.Pro54Arg	missense	Exon 2 of 2	NP_061111.1	Q9NRB3
	CHST12	NM_001243794.2		c.161C>G	p.Pro54Arg	missense	Exon 2 of 2	NP_001230723.1	Q9NRB3
	CHST12	NM_001243795.2		c.161C>G	p.Pro54Arg	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.161C>G	p.Pro54Arg	missense	Exon 2 of 2	ENSP00000481912.1	Q9NRB3
	CHST12	ENST00000258711.7	TSL:1	c.161C>G	p.Pro54Arg	missense	Exon 2 of 2	ENSP00000258711.6	Q9NRB3
	CHST12	ENST00000852327.1		c.161C>G	p.Pro54Arg	missense	Exon 2 of 2	ENSP00000522386.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461482 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.058
DANN	Benign	0.71
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.025
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.042
Sift	Benign	0.56	T
Sift4G	Benign	0.60	T
Polyphen		0.24	B
Vest4		0.12
MutPred		0.19		Loss of sheet (P = 0.0483)
MVP		0.43
MPC		0.55
ClinPred		0.12	T
GERP RS		-4.0
Varity_R		0.038
gMVP		0.32
Mutation Taster		=95/5	polymorphism

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: rs563115579; hg19: chr7-2472435;