3-4467058-C-A

Variant names:

• chr3-4467058-C-A
• NM_182760.4:c.188G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182760.4(SUMF1):​c.188G>T​(p.Ser63Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,413,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S63N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SUMF1 NM_182760.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

Genes affected

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

LOC124909340 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3510297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.188G>T	p.Ser63Ile	missense_variant	Exon 1 of 9	ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.188G>T	p.Ser63Ile	missense_variant	Exon 1 of 9	1	NM_182760.4	ENSP00000272902.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1413338 Hom.: 0 Cov.: 39 AF XY: 0.00000143 AC XY: 1 AN XY: 698296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.85	D;T;T;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Uncertain	0.72	D
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.052	T;T;D;D
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.94	P;.;D;.
Vest4		0.40
MutPred		0.28		Loss of glycosylation at S63 (P = 0.0046);Loss of glycosylation at S63 (P = 0.0046);Loss of glycosylation at S63 (P = 0.0046);Loss of glycosylation at S63 (P = 0.0046);
MVP		0.94
MPC		0.21
ClinPred		0.87	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-4508742;