8-69563986-C-T

Variant names:

• chr8-69563986-C-T
• NM_001128205.2:c.11C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128205.2(SULF1):​c.11C>T​(p.Ser4Phe) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S4A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SULF1 NM_001128205.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.811
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19264823).

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.11C>T	p.Ser4Phe	missense	Exon 5 of 23	NP_001121677.1	Q8IWU6
	SULF1	NM_001412828.1		c.11C>T	p.Ser4Phe	missense	Exon 5 of 22	NP_001399757.1
	SULF1	NM_001412829.1		c.11C>T	p.Ser4Phe	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.11C>T	p.Ser4Phe	missense	Exon 5 of 23	ENSP00000385704.4	Q8IWU6
	SULF1	ENST00000419716.7	TSL:1	c.11C>T	p.Ser4Phe	missense	Exon 4 of 22	ENSP00000390315.3	Q8IWU6
	SULF1	ENST00000458141.6	TSL:1	c.11C>T	p.Ser4Phe	missense	Exon 4 of 22	ENSP00000403040.2	Q8IWU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.048	D
MutationAssessor	Benign	1.4	L
PhyloP100		0.81
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.019	B
Vest4		0.26
MutPred		0.43		Loss of disorder (P = 0.0034)
MVP		0.58
MPC		0.32
ClinPred		0.66	D
GERP RS		4.0
PromoterAI		0.0041	Neutral
Varity_R		0.079
gMVP		0.61
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr8-70476221;