Genetic Variant CHST13:p.His221Tyr (chr3-126542213-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

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]

CHST13 links:

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

C3orf22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.661C>T	p.His221Tyr	missense_variant	Exon 3 of 3	ENST00000319340.7	NP_690849.1	Q8NET6-1
C3orf22	NR_130715.2 link	n.632+7324G>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST13	ENST00000319340.7 link	c.661C>T	p.His221Tyr	missense_variant	Exon 3 of 3	1	NM_152889.3	ENSP00000317404.2		Q8NET6-1
C3orf22	ENST00000505070.5 link	n.286+7324G>A		intron_variant	Intron 4 of 5	2		ENSP00000422064.1		Q8N5N4-2

Frequencies

GnomAD3 genomes

AF:

0.0000595

AC:

AN:

151342

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

91828

Hom.:

AF XY:

0.0000186

AC XY:

AN XY:

53832

show subpopulations

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 SAS 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:

AN:

1309560

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

646592

show subpopulations

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:

0.0000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000220

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000594

AC:

AN:

151450

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

74014

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000280

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.661C>T (p.H221Y) alteration is located in exon 3 (coding exon 3) of the CHST13 gene. This alteration results from a C to T substitution at nucleotide position 661, causing the histidine (H) at amino acid position 221 to be replaced by a tyrosine (Y). 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

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

0.14

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.89

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.34

Sift

Uncertain

0.017

Sift4G

Benign

0.061

Polyphen

0.99

Vest4

0.19

MutPred

0.47

Loss of disorder (P = 0.0578);

MVP

0.72

MPC

1.8

ClinPred

0.43

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over