7-56073066-CTT-C

Position:

• chr7-56073066-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015411.4(SUMF2):​c.296_297del​(p.Phe99CysfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.00175 in 1,614,192 control chromosomes in the GnomAD database, including 50 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0094 (20 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (30 hom.)
• Consequence: SUMF2 NM_015411.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.18

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 -10 ACMG points.

• BP6: Variant 7-56073066-CTT-C is Benign according to our data. Variant chr7-56073066-CTT-C is described in ClinVar as [Benign]. Clinvar id is 709121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00936 (1425/152312) while in subpopulation AFR AF= 0.0318 (1322/41558). AF 95% confidence interval is 0.0304. There are 20 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF2	NM_015411.4	c.296_297del	p.Phe99CysfsTer3	frameshift_variant	3/9	ENST00000434526.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF2	ENST00000434526.8	c.296_297del	p.Phe99CysfsTer3	frameshift_variant	3/9	1	NM_015411.4	P2

Frequencies

GnomAD3 genomes AF: 0.00932 AC: 1419 AN: 152194 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00251 AC: 630 AN: 251488 Hom.: 12 AF XY: 0.00199 AC XY: 270 AN XY: 135920

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000961 AC: 1405 AN: 1461880 Hom.: 30 AF XY: 0.000835 AC XY: 607 AN XY: 727242

Gnomad4 AFR exome AF: 0.0344

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00936 AC: 1425 AN: 152312 Hom.: 20 Cov.: 31 AF XY: 0.00918 AC XY: 684 AN XY: 74484

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00110 Hom.: 2

Bravo AF: 0.0106

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs146946713; hg19: chr7-56140759;