dbSNP rs900044566: CHST12:p.Asp57Asn (chr7-2432808-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018641.5(CHST12):c.169G>A(p.Asp57Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,538 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D57Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHST12
NM_018641.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

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=0.10170016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST12	NM_018641.5 link	c.169G>A	p.Asp57Asn	missense_variant	Exon 2 of 2	ENST00000618655.2	NP_061111.1	Q9NRB3A0A024R860

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHST12	ENST00000618655.2 link	c.169G>A	p.Asp57Asn	missense_variant	Exon 2 of 2	1	NM_018641.5	ENSP00000481912.1	Q9NRB3
CHST12	ENST00000258711.7 link	c.169G>A	p.Asp57Asn	missense_variant	Exon 2 of 2	1		ENSP00000258711.6	Q9NRB3
CHST12	ENST00000432336.1 link	c.169G>A	p.Asp57Asn	missense_variant	Exon 2 of 2	2		ENSP00000411207.1	C9J991

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250412

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461538

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727094

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

DANN

Benign

0.76

DEOGEN2

Benign

0.0018

T;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.53

T;.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.15

.;N;N

REVEL

Benign

0.094

Sift

Benign

0.67

.;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.057

B;B;.

Vest4

0.087

MutPred

0.14

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.59

MPC

0.54

ClinPred

0.071

GERP RS

4.0

Varity_R

0.090

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over