8-69586473-GGC-TCA

Variant names:

• chr8-69586473-GGC-TCA
• NM_001128205.2:c.529_531delGGCinsTCA
• SULF1 p.Gly177Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_001412844.1(SULF1):​c.3_5delGGCinsTCA​(p.MetAla1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULF1 NM_001412844.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

SULF1 (HGNC:20391): (sulfatase 1) This gene encodes an extracellular heparan sulfate endosulfatase. The encoded enzyme selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans (HSPGs). The enzyme is secreted through the Golgi and is subsequently localized to the cell surface. The expression of this gene may be down-regulated in several types of cancer, including hepatocellular (HCC), ovarian and breast cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 7 codons. Genomic position: 69586489. Lost 0.009 part of the original CDS.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001412844.1. 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
	SULF1	NM_001128205.2	MANE Select	c.529_531delGGCinsTCA	p.Gly177Ser	missense	N/A	NP_001121677.1	Q8IWU6
	SULF1	NM_001412844.1		c.3_5delGGCinsTCA	p.MetAla1?	start_lost	N/A	NP_001399773.1
	SULF1	NM_001412845.1		c.3_5delGGCinsTCA	p.MetAla1?	start_lost	N/A	NP_001399774.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.529_531delGGCinsTCA	p.Gly177Ser	missense	N/A	ENSP00000385704.4	Q8IWU6
	SULF1	ENST00000419716.7	TSL:1	c.529_531delGGCinsTCA	p.Gly177Ser	missense	N/A	ENSP00000390315.3	Q8IWU6
	SULF1	ENST00000458141.6	TSL:1	c.529_531delGGCinsTCA	p.Gly177Ser	missense	N/A	ENSP00000403040.2	Q8IWU6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-70498708;