rs218034

Positions:

• chr3-4349180-G-A
• chr3-4349180-G-T

Variant summary

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

The XM_011533624.4(SUMF1):​c.1014+27150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,140 control chromosomes in the GnomAD database, including 46,222 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 0.77 (46222 hom., cov: 32)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	XM_011533624.4	c.1014+27150C>T		intron_variant
SUMF1	XM_011533625.4	c.1014+27150C>T		intron_variant
SUMF1	XM_017006252.3	c.954+61685C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000448413.5	c.1014+27150C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117767 AN: 152022 Hom.: 46161 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.775 AC: 117887 AN: 152140 Hom.: 46222 Cov.: 32 AF XY: 0.777 AC XY: 57770 AN XY: 74368

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.786

Alfa AF: 0.741 Hom.: 5257

Bravo AF: 0.786

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs218034; hg19: chr3-4390864;