NM_001394073.1:c.975A>C

Variant names:

• chrX-132708467-T-G
• rs143752287
• NM_001394073.1:c.975A>C

Variant summary

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

The NM_001394073.1(HS6ST2):​c.975A>C​(p.Ala325Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,067,039 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. A325A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: HS6ST2 NM_001394073.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 0 publications found

Genes affected

HS6ST2 (HGNC:19133): (heparan sulfate 6-O-sulfotransferase 2) Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HS6ST2 Gene-Disease associations (from GenCC):

• Paganini-Miozzo syndrome

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.975A>C	p.Ala325Ala	synonymous_variant	Exon 3 of 5	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7	c.975A>C	p.Ala325Ala	synonymous_variant	Exon 3 of 5	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1067039 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 342045

African (AFR) AF: 0.00 AC: 0 AN: 25613

American (AMR) AF: 0.00 AC: 0 AN: 31575

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18715

East Asian (EAS) AF: 0.00 AC: 0 AN: 29086

South Asian (SAS) AF: 0.00 AC: 0 AN: 49443

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 824614

Other (OTH) AF: 0.00 AC: 0 AN: 44860

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs143752287; hg19: chrX-131842495;