3-4420014-C-T

Variant names:

• chr3-4420014-C-T
• rs711666
• NM_182760.4:c.602+50G>A

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.602+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 1,485,362 control chromosomes in the GnomAD database, including 713,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (64276 hom., cov: 32)
  • Exomes 𝑓: 0.99 (649695 hom.)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.305
• Publications: 4 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=-0.84).
• BP6: Variant 3-4420014-C-T is Benign according to our data. Variant chr3-4420014-C-T is described in ClinVar as Benign. ClinVar VariationId is 263009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 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.602+50G>A		intron	N/A	NP_877437.2
	SUMF1	NM_001164675.2		c.602+50G>A		intron	N/A	NP_001158147.1	Q8NBK3-5
	SUMF1	NM_001164674.2		c.527+50G>A		intron	N/A	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.602+50G>A		intron	N/A	ENSP00000272902.5	Q8NBK3-1
	SUMF1	ENST00000405420.2	TSL:1	c.602+50G>A		intron	N/A	ENSP00000384977.2	Q8NBK3-5
	SUMF1	ENST00000948922.1		c.623+50G>A		intron	N/A	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138393 AN: 152112 Hom.: 64265 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.948

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.927

GnomAD2 exomes AF: 0.968 AC: 240485 AN: 248362 AF XY: 0.972

Gnomad AFR exome AF: 0.689

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.994

Gnomad EAS exome AF: 0.980

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.986 AC: 1314453 AN: 1333132 Hom.: 649695 Cov.: 19 AF XY: 0.986 AC XY: 660498 AN XY: 670114

African (AFR) AF: 0.689 AC: 21272 AN: 30854

American (AMR) AF: 0.983 AC: 43551 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25128 AN: 25280

East Asian (EAS) AF: 0.987 AC: 38564 AN: 39062

South Asian (SAS) AF: 0.946 AC: 78930 AN: 83406

European-Finnish (FIN) AF: 1.00 AC: 53229 AN: 53252

Middle Eastern (MID) AF: 0.980 AC: 5415 AN: 5524

European-Non Finnish (NFE) AF: 0.998 AC: 993754 AN: 995280

Other (OTH) AF: 0.972 AC: 54610 AN: 56162

GnomAD4 genome AF: 0.909 AC: 138452 AN: 152230 Hom.: 64276 Cov.: 32 AF XY: 0.911 AC XY: 67821 AN XY: 74432

African (AFR) AF: 0.698 AC: 28960 AN: 41486

American (AMR) AF: 0.966 AC: 14780 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3457 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5088 AN: 5176

South Asian (SAS) AF: 0.948 AC: 4574 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10600 AN: 10604

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67840 AN: 68042

Other (OTH) AF: 0.924 AC: 1956 AN: 2116

Alfa AF: 0.886 Hom.: 28577

Bravo AF: 0.897

Asia WGS AF: 0.943 AC: 3281 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Multiple sulfatase deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.59
DANN	Benign	0.68
PhyloP100		-0.30
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: rs711666; hg19: chr3-4461698;