chr3-4389164-C-T

Position:

• chr3-4389164-C-T

Variant summary

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

The NM_182760.4(SUMF1):​c.955-12775G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,908 control chromosomes in the GnomAD database, including 25,972 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 0.58 (25972 hom., cov: 31)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	NM_182760.4	c.955-12775G>A		intron_variant		ENST00000272902.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000272902.10	c.955-12775G>A		intron_variant		1	NM_182760.4	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88349 AN: 151788 Hom.: 25927 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.582 AC: 88455 AN: 151908 Hom.: 25972 Cov.: 31 AF XY: 0.581 AC XY: 43154 AN XY: 74248

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.608

Alfa AF: 0.562 Hom.: 47284

Bravo AF: 0.588

Asia WGS AF: 0.476 AC: 1652 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.51

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: rs7641926; hg19: chr3-4430848;