3-126542120-C-T

Variant names:

• chr3-126542120-C-T
• rs1287859275
• NM_152889.3:c.568C>T

Variant summary

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

The NM_152889.3(CHST13):​c.568C>T​(p.Arg190Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R190G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CHST13 NM_152889.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

Genes affected

CHST13 (HGNC:21755): (carbohydrate sulfotransferase 13) 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 the C4 hydroxyl of beta-1,4-linked N-acetylgalactosamine (GalNAc) flanked by glucuronic acid residue in chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. [provided by RefSeq, Aug 2011]

C3orf22 (HGNC:28534): (chromosome 3 open reading frame 22)

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_152889.3. 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
	CHST13	NM_152889.3	MANE Select	c.568C>T	p.Arg190Cys	missense	Exon 3 of 3	NP_690849.1	Q8NET6-1
	C3orf22	NR_130715.2		n.632+7417G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST13	ENST00000319340.7	TSL:1 MANE Select	c.568C>T	p.Arg190Cys	missense	Exon 3 of 3	ENSP00000317404.2	Q8NET6-1
	C3orf22	ENST00000505070.5	TSL:2	n.286+7417G>A		intron	N/A	ENSP00000422064.1	Q8N5N4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424896 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 708904

African (AFR) AF: 0.00 AC: 0 AN: 30718

American (AMR) AF: 0.00 AC: 0 AN: 42716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25064

East Asian (EAS) AF: 0.00 AC: 0 AN: 37078

South Asian (SAS) AF: 0.00 AC: 0 AN: 84294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098134

Other (OTH) AF: 0.00 AC: 0 AN: 58626

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.59
Sift	Benign	0.051	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.51		Loss of MoRF binding (P = 0.002)
MVP		0.85
MPC		2.0
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.71
Mutation Taster		=76/24	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: rs1287859275; hg19: chr3-126260963;