16-71537272-C-T

Variant summary

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

The NM_001166395.2(CHST4):c.595C>T(p.His199Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

CHST4
NM_001166395.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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=0.074674964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST4	NM_001166395.2 linkuse as main transcript	c.595C>T	p.His199Tyr	missense_variant	2/2	ENST00000539698.4
CHST4	NM_005769.2 linkuse as main transcript	c.595C>T	p.His199Tyr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST4	ENST00000539698.4 linkuse as main transcript	c.595C>T	p.His199Tyr	missense_variant	2/2	1	NM_001166395.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251384

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000173

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:

0.0000301

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000201

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000204

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

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

Feb 28, 2024

The c.595C>T (p.H199Y) alteration is located in exon 2 (coding exon 1) of the CHST4 gene. This alteration results from a C to T substitution at nucleotide position 595, causing the histidine (H) at amino acid position 199 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

0.099

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.52

D;D

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.070

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.24

Sift

Benign

0.037

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.024

B;B

Vest4

0.13

MVP

0.72

MPC

0.22

ClinPred

0.038

GERP RS

3.7

Varity_R

0.13

gMVP

0.35

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