NM_004807.3:c.1194G>C

Variant names:

• chr2-128268204-C-G
• rs370255491
• NM_004807.3:c.1194G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004807.3(HS6ST1):​c.1194G>C​(p.Val398Val) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V398V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HS6ST1 NM_004807.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

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]

HS6ST1 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypogonadotropic hypogonadism 15 with or without anosmia

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.65 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004807.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST1	NM_004807.3	MANE Select	c.1194G>C	p.Val398Val	synonymous	Exon 2 of 2	NP_004798.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST1	ENST00000259241.7	TSL:1 MANE Select	c.1194G>C	p.Val398Val	synonymous	Exon 2 of 2	ENSP00000259241.6	O60243-1
	HS6ST1	ENST00000469019.1	TSL:4	n.361-21679G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.3
DANN	Benign	0.56
PhyloP100		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	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: rs370255491; hg19: chr2-129025778;