NM_182760.4:c.1116T>C

Variant names:

• chr3-4362153-A-G
• rs2633852
• NM_182760.4:c.1116T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182760.4(SUMF1):​c.1116T>C​(p.Thr372Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,613,514 control chromosomes in the GnomAD database, including 284,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35126 hom., cov: 34)
  • Exomes 𝑓: 0.58 (249772 hom.)
• Consequence: SUMF1 NM_182760.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.0940
• Publications: 29 publications found

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]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-4362153-A-G is Benign according to our data. Variant chr3-4362153-A-G is described in ClinVar as Benign. ClinVar VariationId is 96559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182760.4. 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
	SUMF1	NM_182760.4	MANE Select	c.1116T>C	p.Thr372Thr	synonymous	Exon 9 of 9	NP_877437.2
	SUMF1	NM_001164675.2		c.1056T>C	p.Thr352Thr	synonymous	Exon 8 of 8	NP_001158147.1
	SUMF1	NM_001164674.2		c.1041T>C	p.Thr347Thr	synonymous	Exon 8 of 8	NP_001158146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000272902.10	TSL:1 MANE Select	c.1116T>C	p.Thr372Thr	synonymous	Exon 9 of 9	ENSP00000272902.5
	SUMF1	ENST00000405420.2	TSL:1	c.1056T>C	p.Thr352Thr	synonymous	Exon 8 of 8	ENSP00000384977.2
	SUMF1	ENST00000948922.1		c.1137T>C	p.Thr379Thr	synonymous	Exon 9 of 9	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101084 AN: 152050 Hom.: 35060 Cov.: 34

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.664

GnomAD2 exomes AF: 0.643 AC: 160356 AN: 249294 AF XY: 0.638

Gnomad AFR exome AF: 0.869

Gnomad AMR exome AF: 0.744

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.765

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.578 AC: 845195 AN: 1461346 Hom.: 249772 Cov.: 46 AF XY: 0.582 AC XY: 422914 AN XY: 726978

African (AFR) AF: 0.874 AC: 29274 AN: 33476

American (AMR) AF: 0.731 AC: 32698 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 15723 AN: 26132

East Asian (EAS) AF: 0.773 AC: 30684 AN: 39690

South Asian (SAS) AF: 0.735 AC: 63424 AN: 86244

European-Finnish (FIN) AF: 0.574 AC: 30643 AN: 53378

Middle Eastern (MID) AF: 0.637 AC: 3645 AN: 5720

European-Non Finnish (NFE) AF: 0.542 AC: 602644 AN: 1111606

Other (OTH) AF: 0.604 AC: 36460 AN: 60378

GnomAD4 genome AF: 0.665 AC: 101212 AN: 152168 Hom.: 35126 Cov.: 34 AF XY: 0.670 AC XY: 49827 AN XY: 74380

African (AFR) AF: 0.858 AC: 35652 AN: 41556

American (AMR) AF: 0.691 AC: 10573 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3468

East Asian (EAS) AF: 0.758 AC: 3911 AN: 5160

South Asian (SAS) AF: 0.753 AC: 3631 AN: 4824

European-Finnish (FIN) AF: 0.584 AC: 6176 AN: 10578

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36951 AN: 67970

Other (OTH) AF: 0.668 AC: 1413 AN: 2114

Alfa AF: 0.592 Hom.: 43556

Bravo AF: 0.683

Asia WGS AF: 0.781 AC: 2715 AN: 3478

EpiCase AF: 0.557

EpiControl AF: 0.565

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Multiple sulfatase deficiency (5)
-	-	5	not specified (5)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.094
Mutation Taster		=100/0	polymorphism (auto)

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: rs2633852; hg19: chr3-4403837; COSMIC: COSV55991868;