16-22915392-C-A

Variant names:

• chr16-22915392-C-A
• NM_006043.2:c.934C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006043.2(HS3ST2):​c.934C>A​(p.Pro312Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HS3ST2 NM_006043.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

HS3ST2 (HGNC:5195): (heparan sulfate-glucosamine 3-sulfotransferase 2) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. This gene is expressed predominantly in brain and may play a role in the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006043.2. 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
	HS3ST2	NM_006043.2	MANE Select	c.934C>A	p.Pro312Thr	missense	Exon 2 of 2	NP_006034.1	Q9Y278

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST2	ENST00000261374.4	TSL:1 MANE Select	c.934C>A	p.Pro312Thr	missense	Exon 2 of 2	ENSP00000261374.3	Q9Y278
	HS3ST2	ENST00000473392.1	TSL:5	n.*736C>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000454505.1	H3BMR2
	HS3ST2	ENST00000473392.1	TSL:5	n.*736C>A		3_prime_UTR	Exon 4 of 4	ENSP00000454505.1	H3BMR2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.020	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.54		Loss of catalytic residue at P312 (P = 0.0057)
MVP		0.88
MPC		2.3
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.64
gMVP		0.92

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

Other links and lift over

hg19: chr16-22926713;