16-71537146-A-T

Variant names:

• chr16-71537146-A-T
• rs1007648187
• NM_001166395.2:c.469A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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. S157N) has been classified as Likely benign.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166395.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST4	NM_001166395.2	MANE Select	c.469A>T	p.Ser157Cys	missense	Exon 2 of 2	NP_001159867.1	Q8NCG5
	CHST4	NM_005769.2		c.469A>T	p.Ser157Cys	missense	Exon 2 of 2	NP_005760.1	Q8NCG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST4	ENST00000539698.4	TSL:1 MANE Select	c.469A>T	p.Ser157Cys	missense	Exon 2 of 2	ENSP00000441204.3	Q8NCG5
	CHST4	ENST00000338482.5	TSL:4	c.469A>T	p.Ser157Cys	missense	Exon 3 of 3	ENSP00000341206.5	Q8NCG5
	CHST4	ENST00000866592.1		c.469A>T	p.Ser157Cys	missense	Exon 2 of 2	ENSP00000536651.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.23	T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.4	L
PhyloP100		-0.33
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.041	D
Polyphen		0.95	P
Vest4		0.21
MutPred		0.61		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

Other links and lift over

dbSNP: rs1007648187; hg19: chr16-71571049;