Genetic Variant CHST4:p.Ala18Ser (chr16-71536729-G-T) – 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_001166395.2(CHST4):c.52G>T(p.Ala18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,492,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CHST4
NM_001166395.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.320

Variant links:

Genes affected

CHST4 (HGNC:1972): (carbohydrate sulfotransferase 4) This gene encodes an N-acetylglucosamine 6-O sulfotransferase. The encoded enzyme transfers sulfate from 3'phosphoadenosine 5'phospho-sulfate to the 6-hydroxyl group of N-acetylglucosamine on glycoproteins. This protein is localized to the Golgi and is involved in the modification of glycan structures on ligands of the lymphocyte homing receptor L-selectin. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]

CHST4 links:

ZNF19 (HGNC:12981): (zinc finger protein 19) The protein encoded by this gene contains a zinc finger, a nucleic acid-binding domain present in many transcription factors. This gene is located in a region next to ZNF23, a gene also encoding a zinc finger protein, on chromosome 16. [provided by RefSeq, Jul 2008]

ZNF19 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=0.14512506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST4	NM_001166395.2 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 2	ENST00000539698.4	NP_001159867.1	Q8NCG5
CHST4	NM_005769.2 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 2		NP_005760.1	Q8NCG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST4	ENST00000539698.4 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 2	1	NM_001166395.2	ENSP00000441204.3		Q8NCG5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1340248

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

653430

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:

0.0000158

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.49e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52G>T (p.A18S) alteration is located in exon 2 (coding exon 1) of the CHST4 gene. This alteration results from a G to T substitution at nucleotide position 52, causing the alanine (A) at amino acid position 18 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

5.6

DANN

Benign

0.95

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.48

.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.15

T;T

MetaSVM

Uncertain

-0.068

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.23

Sift

Benign

0.062

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.48

P;P

Vest4

0.18

MutPred

0.37

Loss of catalytic residue at A18 (P = 0.2052);Loss of catalytic residue at A18 (P = 0.2052);

MVP

0.72

MPC

0.21

ClinPred

0.077

GERP RS

2.3

Varity_R

0.039

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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