rs1351950

Positions:

• chr3-4163939-G-A
• chr3-4163939-G-C

Variant summary

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

The XM_011533624.4(SUMF1):​c.1015-95194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,980 control chromosomes in the GnomAD database, including 5,963 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 0.27 (5963 hom., cov: 31)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-95194C>T		intron_variant			XP_011531926.1
SUMF1	XM_017006252.3	c.955-95194C>T		intron_variant			XP_016861741.1
SUMF1	XM_017006253.2	c.940-95194C>T		intron_variant			XP_016861742.1
SUMF1	XM_017006254.3	c.1015-95194C>T		intron_variant			XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	c.1015-95194C>T		intron_variant, NMD_transcript_variant		2		ENSP00000404384

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41470 AN: 151862 Hom.: 5964 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.273 AC: 41470 AN: 151980 Hom.: 5963 Cov.: 31 AF XY: 0.268 AC XY: 19936 AN XY: 74308

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.302

Alfa AF: 0.307 Hom.: 15236

Bravo AF: 0.272

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1351950; hg19: chr3-4205623;