rs317623

Positions:

• chr3-4025185-T-C
• chr3-4025185-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448413.5(SUMF1):​n.1191+43384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,626 control chromosomes in the GnomAD database, including 45,262 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 0.76 (45262 hom., cov: 31)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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]

ENSG00000287720 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102723512	XR_007095788.1	n.946-2809T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1191+43384A>G		intron_variant		2		ENSP00000404384.1
ENSG00000287720	ENST00000661097.1	n.304-2809T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115089 AN: 151510 Hom.: 45257 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.759 AC: 115129 AN: 151626 Hom.: 45262 Cov.: 31 AF XY: 0.763 AC XY: 56550 AN XY: 74136

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.786

Alfa AF: 0.829 Hom.: 100549

Bravo AF: 0.748

Asia WGS AF: 0.852 AC: 2956 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs317623; hg19: chr3-4066869;