6-114057583-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153612.4(HS3ST5):c.715G>A(p.Glu239Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HS3ST5 NM_153612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

Genes affected

HS3ST5 (HGNC:19419): (heparan sulfate-glucosamine 3-sulfotransferase 5) HS3ST5 belongs to a group of heparan sulfate 3-O-sulfotransferases (EC 2.8.2.23) that transfer sulfate from 3-prime-phosphoadenosine 5-prime phosphosulfate (PAPS) to heparan sulfate and heparin (Mochizuki et al., 2003 [PubMed 12740361]).[supplied by OMIM, Mar 2008]

HDAC2-AS2 (HGNC:43590): (HDAC2 and HS3ST5 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38565707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS3ST5	NM_153612.4	c.715G>A	p.Glu239Lys	missense_variant	5/5	ENST00000312719.10
HDAC2-AS2	NR_125845.1	n.1311-31354C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS3ST5	ENST00000312719.10	c.715G>A	p.Glu239Lys	missense_variant	5/5	2	NM_153612.4	P1
HDAC2-AS2	ENST00000519104.5	n.1311-31354C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 03, 2022

The c.715G>A (p.E239K) alteration is located in exon 2 (coding exon 2) of the HS3ST5 gene. This alteration results from a G to A substitution at nucleotide position 715, causing the glutamic acid (E) at amino acid position 239 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	0.070
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.12	B;B
Vest4		0.72
MutPred		0.64		Gain of MoRF binding (P = 0.007);Gain of MoRF binding (P = 0.007);
MVP		0.39
MPC		0.27
ClinPred		0.80	D
GERP RS		6.1
Varity_R		0.38
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-114378747; COSMIC: COSV57134965;