3-4403105-G-A

Position:

• chr3-4403105-G-A

Variant summary

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

The ENST00000272902.10(SUMF1):​c.954+7760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 152,236 control chromosomes in the GnomAD database, including 106 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 0.029 (106 hom., cov: 32)
• Consequence: SUMF1 ENST00000272902.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.954+7760C>T		intron_variant		ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.954+7760C>T		intron_variant		1	NM_182760.4	ENSP00000272902	P1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4453 AN: 152118 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0293 AC: 4459 AN: 152236 Hom.: 106 Cov.: 32 AF XY: 0.0290 AC XY: 2158 AN XY: 74434

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0174 Hom.: 12

Bravo AF: 0.0324

Asia WGS AF: 0.00924 AC: 32 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	2.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3852047; hg19: chr3-4444789;