rs13238899

Positions:

• chr7-56072925-T-G

Variant summary

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

The ENST00000434526.8(SUMF2):​c.225-72T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,127,292 control chromosomes in the GnomAD database, including 4,346 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 0.083 (623 hom., cov: 32)
  • Exomes 𝑓: 0.075 (3723 hom.)
• Consequence: SUMF2 ENST00000434526.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

Genes affected

SUMF2 (HGNC:20415): (sulfatase modifying factor 2) The catalytic sites of sulfatases are only active if they contain a unique amino acid, C-alpha-formylglycine (FGly). The FGly residue is posttranslationally generated from a cysteine by enzymes with FGly-generating activity. The gene described in this record is a member of the sulfatase-modifying factor family and encodes a protein with a DUF323 domain that localizes to the lumen of the endoplasmic reticulum. This protein has low levels of FGly-generating activity but can heterodimerize with another family member - a protein with high levels of FGly-generating activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF2	NM_015411.4	c.225-72T>G		intron_variant		ENST00000434526.8	NP_056226.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF2	ENST00000434526.8	c.225-72T>G		intron_variant		1	NM_015411.4	ENSP00000400922	P2

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12564 AN: 152096 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0748 AC: 72970 AN: 975078 Hom.: 3723 AF XY: 0.0755 AC XY: 37705 AN XY: 499534

Gnomad4 AFR exome AF: 0.0920

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0557

Gnomad4 OTH exome AF: 0.0715

GnomAD4 genome AF: 0.0826 AC: 12579 AN: 152214 Hom.: 623 Cov.: 32 AF XY: 0.0882 AC XY: 6566 AN XY: 74418

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0668 Hom.: 508

Bravo AF: 0.0827

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Benign	0.88

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: rs13238899; hg19: chr7-56140618; COSMIC: COSV51915541; COSMIC: COSV51915541;