NM_182760.4:c.*11A>T

Variant names:

• chr3-4362133-T-A
• rs2633851
• NM_182760.4:c.*11A>T

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.*11A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,611,076 control chromosomes in the GnomAD database, including 276,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31464 hom., cov: 33)
  • Exomes 𝑓: 0.57 (245449 hom.)
• Consequence: SUMF1 NM_182760.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.812
• Publications: 16 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=-0.79).
• BP6: Variant 3-4362133-T-A is Benign according to our data. Variant chr3-4362133-T-A is described in ClinVar as Benign. ClinVar VariationId is 96558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 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.*11A>T		3_prime_UTR	Exon 9 of 9	NP_877437.2
	SUMF1	NM_001164675.2		c.*11A>T		3_prime_UTR	Exon 8 of 8	NP_001158147.1
	SUMF1	NM_001164674.2		c.*11A>T		3_prime_UTR	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.*11A>T		3_prime_UTR	Exon 9 of 9	ENSP00000272902.5
	SUMF1	ENST00000405420.2	TSL:1	c.*11A>T		3_prime_UTR	Exon 8 of 8	ENSP00000384977.2
	SUMF1	ENST00000948922.1		c.*11A>T		3_prime_UTR	Exon 9 of 9	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96440 AN: 151888 Hom.: 31421 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.641

GnomAD2 exomes AF: 0.634 AC: 158118 AN: 249370 AF XY: 0.631

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.738

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.764

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.575 AC: 838431 AN: 1459070 Hom.: 245449 Cov.: 34 AF XY: 0.578 AC XY: 419951 AN XY: 725950

African (AFR) AF: 0.769 AC: 25723 AN: 33444

American (AMR) AF: 0.725 AC: 32399 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 15547 AN: 26110

East Asian (EAS) AF: 0.773 AC: 30663 AN: 39666

South Asian (SAS) AF: 0.735 AC: 63360 AN: 86192

European-Finnish (FIN) AF: 0.574 AC: 30622 AN: 53350

Middle Eastern (MID) AF: 0.628 AC: 3517 AN: 5604

European-Non Finnish (NFE) AF: 0.541 AC: 600693 AN: 1109732

Other (OTH) AF: 0.596 AC: 35907 AN: 60272

GnomAD4 genome AF: 0.635 AC: 96534 AN: 152006 Hom.: 31464 Cov.: 33 AF XY: 0.641 AC XY: 47628 AN XY: 74300

African (AFR) AF: 0.758 AC: 31461 AN: 41516

American (AMR) AF: 0.678 AC: 10356 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2144 AN: 3466

East Asian (EAS) AF: 0.758 AC: 3905 AN: 5154

South Asian (SAS) AF: 0.751 AC: 3623 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6137 AN: 10550

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36819 AN: 67908

Other (OTH) AF: 0.645 AC: 1362 AN: 2112

Alfa AF: 0.497 Hom.: 2497

Bravo AF: 0.649

Asia WGS AF: 0.770 AC: 2679 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Multiple sulfatase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.58
PhyloP100		0.81
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: rs2633851; hg19: chr3-4403817; COSMIC: COSV55991857;