chr3-126542213-C-T

Variant names:

• chr3-126542213-C-T
• rs766907791
• NM_152889.3:c.661C>T

Variant summary

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

The NM_152889.3(CHST13):​c.661C>T​(p.His221Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H221Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CHST13 NM_152889.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• 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.661C>T	p.His221Tyr	missense	Exon 3 of 3	NP_690849.1	Q8NET6-1
	C3orf22	NR_130715.2		n.632+7324G>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.661C>T	p.His221Tyr	missense	Exon 3 of 3	ENSP00000317404.2	Q8NET6-1
	C3orf22	ENST00000505070.5	TSL:2	n.286+7324G>A		intron	N/A	ENSP00000422064.1	Q8N5N4-2

Frequencies

GnomAD3 genomes AF: 0.0000595 AC: 9 AN: 151342 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000327 AC: 3 AN: 91828 AF XY: 0.0000186

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: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000183 AC: 24 AN: 1309560 Hom.: 0 Cov.: 34 AF XY: 0.0000217 AC XY: 14 AN XY: 646592

African (AFR) AF: 0.00 AC: 0 AN: 25780

American (AMR) AF: 0.00 AC: 0 AN: 21590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21218

East Asian (EAS) AF: 0.00 AC: 0 AN: 29338

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 0.0000220 AC: 23 AN: 1046872

Other (OTH) AF: 0.00 AC: 0 AN: 53576

GnomAD4 genome AF: 0.0000594 AC: 9 AN: 151450 Hom.: 0 Cov.: 33 AF XY: 0.0000676 AC XY: 5 AN XY: 74014

African (AFR) AF: 0.00 AC: 0 AN: 41482

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67760

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000280 AC: 3

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	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.082
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.017	D
Sift4G	Benign	0.061	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.47		Loss of disorder (P = 0.0578)
MVP		0.72
MPC		1.8
ClinPred		0.43	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.55
Mutation Taster		=94/6	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: rs766907791; hg19: chr3-126261056;