8-69563986-C-T

Position:

• chr8-69563986-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.11C>T	p.Ser4Phe	missense_variant	5/23	ENST00000402687.9	NP_001121677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF1	ENST00000402687.9	c.11C>T	p.Ser4Phe	missense_variant	5/23	1	NM_001128205.2	ENSP00000385704	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.11C>T (p.S4F) alteration is located in exon 5 (coding exon 1) of the SULF1 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the serine (S) at amino acid position 4 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T;T;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.74	T;T;.;T;.;.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.048	D
MutationAssessor	Benign	1.4	.;L;L;.;L;L;.;.;.
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.2	D;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;T;D;D;T;T;T
Sift4G	Pathogenic	0.0	D;T;T;T;T;T;T;T;T
Polyphen		0.019	.;B;B;.;B;B;.;.;.
Vest4		0.26, 0.26, 0.22, 0.25
MutPred		0.43		Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);
MVP		0.58
MPC		0.32
ClinPred		0.66	D
GERP RS		4.0
Varity_R		0.079
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-70476221;