rs317608

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-4034252-G-A
• chr3-4034252-G-C
• chr3-4034252-G-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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723512	XR_007095787.1	n.1210+4127G>A		intron_variant	Intron 1 of 1
LOC102723512	XR_007095788.1	n.1004+6200G>A		intron_variant	Intron 2 of 2
SUMF1	XM_017006254.3	c.*477C>T		downstream_gene_variant			XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1191+34317C>T		intron_variant	Intron 9 of 12	2		ENSP00000404384.1
ENSG00000287720	ENST00000654218.1	n.59+6200G>A		intron_variant	Intron 1 of 2
ENSG00000287720	ENST00000661097.1	n.450+4127G>A		intron_variant	Intron 5 of 6

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 v4.3

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

Other links and lift over

dbSNP: rs317608; hg19: chr3-4075936;