chr3-4068016-A-C

Variant names:

• chr3-4068016-A-C
• rs795734
• XM_011533624.4:c.1269T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011533624.4(SUMF1):​c.1269T>G​(p.Phe423Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,072 control chromosomes in the GnomAD database, including 10,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10125 hom., cov: 32)
• Consequence: SUMF1 XM_011533624.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1269T>G	p.Phe423Leu	missense_variant	Exon 10 of 10		XP_011531926.1
SUMF1	XM_017006252.3	c.1209T>G	p.Phe403Leu	missense_variant	Exon 9 of 9		XP_016861741.1
SUMF1	XM_017006253.2	c.1194T>G	p.Phe398Leu	missense_variant	Exon 9 of 9		XP_016861742.1
SUMF1	XM_017006254.3	c.1191+553T>G		intron_variant	Intron 9 of 9		XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1191+553T>G		intron_variant	Intron 9 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54420 AN: 151952 Hom.: 10085 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.358 AC: 54513 AN: 152072 Hom.: 10125 Cov.: 32 AF XY: 0.360 AC XY: 26735 AN XY: 74332

African (AFR) AF: 0.394 AC: 16329 AN: 41454

American (AMR) AF: 0.466 AC: 7120 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2221 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4822

European-Finnish (FIN) AF: 0.283 AC: 2996 AN: 10576

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21527 AN: 67992

Other (OTH) AF: 0.378 AC: 800 AN: 2116

Alfa AF: 0.342 Hom.: 25415

Bravo AF: 0.378

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.0
DANN	Benign	0.75
PhyloP100		0.016
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: rs795734; hg19: chr3-4109700;