Variant chr7-2432854-A-G 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.215A>G(p.Lys72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. K72N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHST12
NM_018641.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.384

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:

Genome browser will be placed here

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=0.08244592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST12	NM_018641.5 linkuse as main transcript	c.215A>G	p.Lys72Arg	missense_variant	2/2	ENST00000618655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHST12	ENST00000618655.2 linkuse as main transcript	c.215A>G	p.Lys72Arg	missense_variant	2/2	1	NM_018641.5	P1
CHST12	ENST00000258711.7 linkuse as main transcript	c.215A>G	p.Lys72Arg	missense_variant	2/2	1		P1
CHST12	ENST00000432336.1 linkuse as main transcript	c.215A>G	p.Lys72Arg	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727086

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 28, 2024

The c.215A>G (p.K72R) alteration is located in exon 2 (coding exon 1) of the CHST12 gene. This alteration results from a A to G substitution at nucleotide position 215, causing the lysine (K) at amino acid position 72 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.5

DANN

Benign

0.93

DEOGEN2

Benign

0.0045

T;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.18

.;N;N

REVEL

Benign

0.056

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.094

B;B;.

Vest4

0.051

MutPred

0.19

Loss of ubiquitination at K72 (P = 0.0074);Loss of ubiquitination at K72 (P = 0.0074);Loss of ubiquitination at K72 (P = 0.0074);

MVP

0.78

MPC

0.42

ClinPred

0.088

GERP RS

-0.48

Varity_R

0.033

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over