6-114057402-A-G

Position:

• chr6-114057402-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153612.4(HS3ST5):​c.896T>C​(p.Ile299Thr) 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. 12/21 in silico tools predict 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: 4.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12736312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST5	NM_153612.4	c.896T>C	p.Ile299Thr	missense_variant	5/5	ENST00000312719.10	NP_705840.2
HDAC2-AS2	NR_125845.1	n.1311-31535A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST5	ENST00000312719.10	c.896T>C	p.Ile299Thr	missense_variant	5/5	2	NM_153612.4	ENSP00000427888	P1
HDAC2-AS2	ENST00000519104.5	n.1311-31535A>G		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

Nov 06, 2023

The c.896T>C (p.I299T) alteration is located in exon 2 (coding exon 2) of the HS3ST5 gene. This alteration results from a T to C substitution at nucleotide position 896, causing the isoleucine (I) at amino acid position 299 to be replaced by a threonine (T). 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	0.27
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.2	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.6	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.55	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.032	B;B
Vest4		0.39
MutPred		0.39		Loss of stability (P = 0.0178);Loss of stability (P = 0.0178);
MVP		0.43
MPC		0.47
ClinPred		0.70	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.69

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: chr6-114378566;