chr7-56072925-T-G

Variant names:

• chr7-56072925-T-G
• rs13238899
• NM_015411.4:c.225-72T>G

Variant summary

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

The NM_015411.4(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 NM_015411.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015411.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	NM_015411.4	MANE Select	c.225-72T>G		intron	N/A	NP_056226.3
	SUMF2	NM_001366648.2		c.225-72T>G		intron	N/A	NP_001353577.1
	SUMF2	NM_001130069.4		c.225-72T>G		intron	N/A	NP_001123541.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	ENST00000434526.8	TSL:1 MANE Select	c.225-72T>G		intron	N/A	ENSP00000400922.3
	SUMF2	ENST00000342190.11	TSL:1	c.225-72T>G		intron	N/A	ENSP00000341938.7
	SUMF2	ENST00000395436.7	TSL:1	c.225-72T>G		intron	N/A	ENSP00000378824.3

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

African (AFR) AF: 0.0920 AC: 2195 AN: 23866

American (AMR) AF: 0.146 AC: 5844 AN: 40030

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 1153 AN: 20254

East Asian (EAS) AF: 0.251 AC: 9339 AN: 37266

South Asian (SAS) AF: 0.110 AC: 7602 AN: 69044

European-Finnish (FIN) AF: 0.102 AC: 5222 AN: 51154

Middle Eastern (MID) AF: 0.0625 AC: 293 AN: 4690

European-Non Finnish (NFE) AF: 0.0557 AC: 38166 AN: 684652

Other (OTH) AF: 0.0715 AC: 3156 AN: 44122

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

African (AFR) AF: 0.0855 AC: 3553 AN: 41556

American (AMR) AF: 0.105 AC: 1603 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1210 AN: 5158

South Asian (SAS) AF: 0.118 AC: 567 AN: 4822

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4071 AN: 68018

Other (OTH) AF: 0.0814 AC: 172 AN: 2114

Alfa AF: 0.0706 Hom.: 1454

Bravo AF: 0.0827

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.5
DANN	Benign	0.88
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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