13-96091062-G-T

Variant names:

• chr13-96091062-G-T
• rs921525067
• NM_153456.4:c.200G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_153456.4(HS6ST3):​c.200G>T​(p.Arg67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,119,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: HS6ST3 NM_153456.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18157572).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4	c.200G>T	p.Arg67Leu	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.200G>T	p.Arg67Leu	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000982 AC: 11 AN: 1119876 Hom.: 0 Cov.: 32 AF XY: 0.00000561 AC XY: 3 AN XY: 535106

African (AFR) AF: 0.00 AC: 0 AN: 22976

American (AMR) AF: 0.00 AC: 0 AN: 8480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14668

East Asian (EAS) AF: 0.00 AC: 0 AN: 26776

South Asian (SAS) AF: 0.00 AC: 0 AN: 27518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3724

European-Non Finnish (NFE) AF: 0.0000106 AC: 10 AN: 943580

Other (OTH) AF: 0.0000223 AC: 1 AN: 44930

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.17
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.18	N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.31	T
Polyphen		0.0010	B
Vest4		0.30
MutPred		0.30		Gain of catalytic residue at P72 (P = 5e-04);
MVP		0.13
MPC		0.66
ClinPred		0.59	D
GERP RS		2.1
Varity_R		0.086
gMVP		0.25
Mutation Taster		=86/14	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

dbSNP: rs921525067; hg19: chr13-96743316;