13-96091221-T-G

Variant names:

• chr13-96091221-T-G
• rs1278564509
• NM_153456.4:c.359T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153456.4(HS6ST3):​c.359T>G​(p.Leu120Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L120P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: HS6ST3 NM_153456.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29268146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST3	NM_153456.4	c.359T>G	p.Leu120Arg	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.359T>G	p.Leu120Arg	missense_variant	Exon 1 of 2	1	NM_153456.4	ENSP00000365895.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425536 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 705930

African (AFR) AF: 0.00 AC: 0 AN: 32562

American (AMR) AF: 0.00 AC: 0 AN: 39492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 37340

South Asian (SAS) AF: 0.00 AC: 0 AN: 81986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093292

Other (OTH) AF: 0.00 AC: 0 AN: 59022

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.056	T
Polyphen		0.14	B
Vest4		0.41
MutPred		0.47		Gain of MoRF binding (P = 0.0647);
MVP		0.082
MPC		1.3
ClinPred		0.75	D
GERP RS		2.7
Varity_R		0.29
gMVP		0.30
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: rs1278564509; hg19: chr13-96743475;