NM_153456.4:c.240G>C

Variant names:

• chr13-96091102-G-C
• NM_153456.4:c.240G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153456.4(HS6ST3):​c.240G>C​(p.Glu80Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. E80A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: HS6ST3 NM_153456.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.107
• Publications: 0 publications found

Genes affected

HS6ST3 (HGNC:19134): (heparan sulfate 6-O-sulfotransferase 3) Heparan sulfate (HS) sulfotransferases, such as HS6ST3, modify HS to generate structures required for interactions between HS and a variety of proteins. These interactions are implicated in proliferation and differentiation, adhesion, migration, inflammation, blood coagulation, and other diverse processes (Habuchi et al., 2000 [PubMed 10644753]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20317188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4	c.240G>C	p.Glu80Asp	missense_variant	Exon 1 of 2	ENST00000376705.4	NP_703157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4	c.240G>C	p.Glu80Asp	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.240G>C (p.E80D) alteration is located in exon 1 (coding exon 1) of the HS6ST3 gene. This alteration results from a G to C substitution at nucleotide position 240, causing the glutamic acid (E) at amino acid position 80 to be replaced by an aspartic acid (D). 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	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.11
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.13
Sift	Benign	0.074	T
Sift4G	Benign	0.54	T
Polyphen		0.059	B
Vest4		0.20
MutPred		0.24		Gain of catalytic residue at P78 (P = 8e-04);
MVP		0.28
MPC		0.48
ClinPred		0.18	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.25
Mutation Taster		=91/9	polymorphism

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: chr13-96743356;