chr3-126542215-C-A

Variant names:

• chr3-126542215-C-A
• rs754370173
• NM_152889.3:c.663C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152889.3(CHST13):​c.663C>A​(p.His221Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,322,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. 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. H221Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: CHST13 NM_152889.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.148

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST13	NM_152889.3	c.663C>A	p.His221Gln	missense_variant	Exon 3 of 3	ENST00000319340.7	NP_690849.1
C3orf22	NR_130715.2	n.632+7322G>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST13	ENST00000319340.7	c.663C>A	p.His221Gln	missense_variant	Exon 3 of 3	1	NM_152889.3	ENSP00000317404.2
C3orf22	ENST00000505070.5	n.286+7322G>T		intron_variant	Intron 4 of 5	2		ENSP00000422064.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000378 AC: 5 AN: 1322838 Hom.: 0 Cov.: 34 AF XY: 0.00000306 AC XY: 2 AN XY: 653842

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000412

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.50e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000186 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.663C>A (p.H221Q) alteration is located in exon 3 (coding exon 3) of the CHST13 gene. This alteration results from a C to A substitution at nucleotide position 663, causing the histidine (H) at amino acid position 221 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.083
Eigen_PC	Benign	-0.0011
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Benign	0.030	D
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.15
MutPred		0.40		Gain of solvent accessibility (P = 0.0074);
MVP		0.78
MPC		1.7
ClinPred		0.58	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs754370173; hg19: chr3-126261058;