rs35083095

Variant names:

• chr3-4362134-T-C
• rs35083095
• NM_182760.4:c.*10A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-4362134-T-C
• chr3-4362134-T-G

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.*10A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,611,632 control chromosomes in the GnomAD database, including 195,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15387 hom., cov: 34)
  • Exomes 𝑓: 0.49 (179807 hom.)
• Consequence: SUMF1 NM_182760.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.18
• Publications: 18 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-4362134-T-C is Benign according to our data. Variant chr3-4362134-T-C is described in ClinVar as Benign. ClinVar VariationId is 96557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 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.*10A>G		3_prime_UTR	Exon 9 of 9	NP_877437.2
	SUMF1	NM_001164675.2		c.*10A>G		3_prime_UTR	Exon 8 of 8	NP_001158147.1	Q8NBK3-5
	SUMF1	NM_001164674.2		c.*10A>G		3_prime_UTR	Exon 8 of 8	NP_001158146.1	Q8NBK3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000272902.10	TSL:1 MANE Select	c.*10A>G		3_prime_UTR	Exon 9 of 9	ENSP00000272902.5	Q8NBK3-1
	SUMF1	ENST00000405420.2	TSL:1	c.*10A>G		3_prime_UTR	Exon 8 of 8	ENSP00000384977.2	Q8NBK3-5
	SUMF1	ENST00000948922.1		c.*10A>G		3_prime_UTR	Exon 9 of 9	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65440 AN: 151908 Hom.: 15383 Cov.: 34

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.473

GnomAD2 exomes AF: 0.503 AC: 125370 AN: 249268 AF XY: 0.503

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.626

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.507

GnomAD4 exome AF: 0.493 AC: 719494 AN: 1459604 Hom.: 179807 Cov.: 35 AF XY: 0.493 AC XY: 358050 AN XY: 726188

African (AFR) AF: 0.216 AC: 7226 AN: 33454

American (AMR) AF: 0.587 AC: 26226 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13740 AN: 26116

East Asian (EAS) AF: 0.625 AC: 24784 AN: 39666

South Asian (SAS) AF: 0.475 AC: 40975 AN: 86196

European-Finnish (FIN) AF: 0.519 AC: 27706 AN: 53346

Middle Eastern (MID) AF: 0.492 AC: 2759 AN: 5610

European-Non Finnish (NFE) AF: 0.493 AC: 546951 AN: 1110216

Other (OTH) AF: 0.483 AC: 29127 AN: 60300

GnomAD4 genome AF: 0.431 AC: 65465 AN: 152028 Hom.: 15387 Cov.: 34 AF XY: 0.435 AC XY: 32356 AN XY: 74312

African (AFR) AF: 0.227 AC: 9417 AN: 41524

American (AMR) AF: 0.527 AC: 8061 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3163 AN: 5152

South Asian (SAS) AF: 0.476 AC: 2294 AN: 4822

European-Finnish (FIN) AF: 0.524 AC: 5522 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33445 AN: 67920

Other (OTH) AF: 0.473 AC: 999 AN: 2112

Alfa AF: 0.459 Hom.: 8549

Bravo AF: 0.428

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		-1.2
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: rs35083095; hg19: chr3-4403818; COSMIC: COSV55991862;