16-71537146-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001166395.2(CHST4):c.469A>T(p.Ser157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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. S157G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST4 NM_001166395.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.325

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST4	NM_001166395.2	c.469A>T	p.Ser157Cys	missense_variant	2/2	ENST00000539698.4
CHST4	NM_005769.2	c.469A>T	p.Ser157Cys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST4	ENST00000539698.4	c.469A>T	p.Ser157Cys	missense_variant	2/2	1	NM_001166395.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.469A>T (p.S157C) alteration is located in exon 2 (coding exon 1) of the CHST4 gene. This alteration results from a A to T substitution at nucleotide position 469, causing the serine (S) at amino acid position 157 to be replaced by a cysteine (C). 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	0.26
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Uncertain	0.65	D;D
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.12	N
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.041	D;D
Polyphen		0.95	P;P
Vest4		0.21
MutPred		0.61		Gain of catalytic residue at S157 (P = 0.203);Gain of catalytic residue at S157 (P = 0.203);
MVP		0.80
MPC		0.61
ClinPred		0.63	D
GERP RS		-7.2
Varity_R		0.24
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71571049;