chr2-128268266-G-C

Variant names:

• chr2-128268266-G-C
• NM_004807.3:c.1132C>G

Variant summary

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

The NM_004807.3(HS6ST1):​c.1132C>G​(p.Arg378Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HS6ST1 NM_004807.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

Genes affected

HS6ST1 (HGNC:5201): (heparan sulfate 6-O-sulfotransferase 1) The protein encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biological activities. This enzyme is a type II integral membrane protein and is responsible for 6-O-sulfation of heparan sulfate. This enzyme does not share significant sequence similarity with other known sulfotransferases. A pseudogene located on chromosome 1 has been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST1	NM_004807.3	c.1132C>G	p.Arg378Gly	missense_variant	Exon 2 of 2	ENST00000259241.7	NP_004798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST1	ENST00000259241.7	c.1132C>G	p.Arg378Gly	missense_variant	Exon 2 of 2	1	NM_004807.3	ENSP00000259241.6
HS6ST1	ENST00000469019.1	n.361-21741C>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459590 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.0010
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.45	B
Vest4		0.46
MutPred		0.52		Gain of loop (P = 0.0045);
MVP		0.83
ClinPred		0.93	D
GERP RS		3.3
Varity_R		0.32
gMVP		0.45

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: chr2-129025840;