chr3-4034252-G-A

Variant names:

• chr3-4034252-G-A
• rs317608
• ENST00000448413.5:n.1191+34317C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448413.5(SUMF1):​n.1191+34317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,120 control chromosomes in the GnomAD database, including 59,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59322 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 6 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: ClinGen, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000287720 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448413.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000448413.5	TSL:2	n.1191+34317C>T		intron	N/A	ENSP00000404384.1	F5GXA0
	ENSG00000287720	ENST00000654218.1		n.59+6200G>A		intron	N/A
	ENSG00000287720	ENST00000661097.1		n.450+4127G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133745 AN: 152002 Hom.: 59287 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.880 AC: 133838 AN: 152120 Hom.: 59322 Cov.: 32 AF XY: 0.882 AC XY: 65606 AN XY: 74360

African (AFR) AF: 0.764 AC: 31671 AN: 41452

American (AMR) AF: 0.926 AC: 14147 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3212 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5176

South Asian (SAS) AF: 0.977 AC: 4712 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9456 AN: 10598

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62575 AN: 68012

Other (OTH) AF: 0.904 AC: 1911 AN: 2114

Alfa AF: 0.891 Hom.: 10251

Bravo AF: 0.874

Asia WGS AF: 0.965 AC: 3356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.60
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs317608;

hg19: chr3-4075936;