Genetic Variant NM_153456.4:c.242G>T (chr13-96091104-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153456.4(HS6ST3):c.242G>T(p.Gly81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000804 in 1,243,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

HS6ST3
NM_153456.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Publications

0 publications found

Variant links:

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]

HS6ST3 links:

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ACMG classification

Classification was made for transcript

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=0.18083996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4 link	c.242G>T	p.Gly81Val	missense_variant	Exon 1 of 2	ENST00000376705.4	NP_703157.2	Q8IZP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST3	ENST00000376705.4 link	c.242G>T	p.Gly81Val	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2		Q8IZP7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.04e-7

AC:

AN:

1243734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

603770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25108

American (AMR)

AF:

0.00

AC:

AN:

15510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17796

East Asian (EAS)

AF:

0.00

AC:

AN:

29488

South Asian (SAS)

AF:

0.00

AC:

AN:

55248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3738

European-Non Finnish (NFE)

AF:

9.87e-7

AC:

AN:

1012728

Other (OTH)

AF:

0.00

AC:

AN:

50950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.242G>T (p.G81V) alteration is located in exon 1 (coding exon 1) of the HS6ST3 gene. This alteration results from a G to T substitution at nucleotide position 242, causing the glycine (G) at amino acid position 81 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.81

PhyloP100

1.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.32

REVEL

Benign

0.11

Sift

Uncertain

0.011

Sift4G

Uncertain

0.011

Polyphen

0.028

Vest4

0.39

MutPred

0.28

Gain of catalytic residue at P78 (P = 0.001);

MVP

0.068

MPC

0.66

ClinPred

0.13

GERP RS

1.0

Varity_R

0.11

gMVP

0.30

Mutation Taster

=91/9

polymorphism

(source)

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

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NM_153456.4:c.242G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over