Variant 7-2432644-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018641.5(CHST12):c.5C>T(p.Thr2Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,605,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CHST12
NM_018641.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Variant links:

Genes affected

CHST12 (HGNC:17423): (carbohydrate sulfotransferase 12) 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 position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin and desulfated dermatan sulfate. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. Alternatively spliced transcript variants differing only in their 5' UTRs have been found for this gene. [provided by RefSeq, Aug 2011]

CHST12 links:

CHST12 (HGNC:):

CHST12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13383389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST12	NM_018641.5 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	2/2	ENST00000618655.2	NP_061111.1	Q9NRB3A0A024R860

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHST12	ENST00000618655.2 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	2/2	1	NM_018641.5	ENSP00000481912.1	Q9NRB3
CHST12	ENST00000258711.7 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	2/2	1		ENSP00000258711.6	Q9NRB3
CHST12	ENST00000432336.1 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	2/2	2		ENSP00000411207.1	C9J991

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

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:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

247770

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1453346

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

721210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.5C>T (p.T2I) alteration is located in exon 2 (coding exon 1) of the CHST12 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the threonine (T) at amino acid position 2 to be replaced by an isoleucine (I). 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

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0076

T;T;.

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.51

T;.;T

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.85

.;N;N

REVEL

Benign

0.049

Sift

Benign

0.042

.;D;D

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.31

B;B;.

Vest4

0.30

MutPred

0.30

Loss of disorder (P = 0.0345);Loss of disorder (P = 0.0345);Loss of disorder (P = 0.0345);

MVP

0.75

MPC

0.68

ClinPred

0.082

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.62

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