3-126542124-C-T

Variant names:

• chr3-126542124-C-T
• NM_152889.3:c.572C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152889.3(CHST13):​c.572C>T​(p.Pro191Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,419,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CHST13 NM_152889.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39449155).

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.572C>T	p.Pro191Leu	missense	Exon 3 of 3	NP_690849.1	Q8NET6-1
	C3orf22	NR_130715.2		n.632+7413G>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.572C>T	p.Pro191Leu	missense	Exon 3 of 3	ENSP00000317404.2	Q8NET6-1
	C3orf22	ENST00000505070.5	TSL:2	n.286+7413G>A		intron	N/A	ENSP00000422064.1	Q8N5N4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1419218 Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1 AN XY: 705690

African (AFR) AF: 0.00 AC: 0 AN: 30282

American (AMR) AF: 0.00 AC: 0 AN: 41918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24922

East Asian (EAS) AF: 0.00 AC: 0 AN: 36624

South Asian (SAS) AF: 0.00 AC: 0 AN: 83838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000365 AC: 4 AN: 1095398

Other (OTH) AF: 0.00 AC: 0 AN: 58310

GnomAD4 genome Cov.: 33

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.81	P
Vest4		0.12
MutPred		0.51		Loss of disorder (P = 0.0375)
MVP		0.79
MPC		1.5
ClinPred		0.98	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.46
Mutation Taster		=84/16	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

hg19: chr3-126260967; COSMIC: COSV60041782;