NM_001128205.2:c.80C>A

Variant names:

• chr8-69564055-C-A
• rs760630163
• NM_001128205.2:c.80C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001128205.2(SULF1):​c.80C>A​(p.Ser27Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S27F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SULF1 NM_001128205.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 1 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128205.2. 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.80C>A	p.Ser27Tyr	missense	Exon 5 of 23	NP_001121677.1	Q8IWU6
	SULF1	NM_001412828.1		c.80C>A	p.Ser27Tyr	missense	Exon 5 of 22	NP_001399757.1
	SULF1	NM_001412829.1		c.80C>A	p.Ser27Tyr	missense	Exon 4 of 21	NP_001399758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.80C>A	p.Ser27Tyr	missense	Exon 5 of 23	ENSP00000385704.4	Q8IWU6
	SULF1	ENST00000419716.7	TSL:1	c.80C>A	p.Ser27Tyr	missense	Exon 4 of 22	ENSP00000390315.3	Q8IWU6
	SULF1	ENST00000458141.6	TSL:1	c.80C>A	p.Ser27Tyr	missense	Exon 4 of 22	ENSP00000403040.2	Q8IWU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.72	P
Vest4		0.74
MutPred		0.50		Loss of disorder (P = 0.0191)
MVP		0.90
MPC		0.37
ClinPred		0.96	D
GERP RS		6.1
PromoterAI		-0.020	Neutral
Varity_R		0.039
gMVP		0.77
Mutation Taster		=72/28	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: rs760630163; hg19: chr8-70476290;