7-56068502-A-G

Variant names:

• chr7-56068502-A-G
• rs1562860017
• NM_015411.4:c.88A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015411.4(SUMF2):​c.88A>G​(p.Met30Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUMF2 NM_015411.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.31
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	NM_015411.4	MANE Select	c.88A>G	p.Met30Val	missense	Exon 2 of 9	NP_056226.3	Q8NBJ7-1
	SUMF2	NM_001366648.2		c.88A>G	p.Met30Val	missense	Exon 2 of 10	NP_001353577.1	C9J660
	SUMF2	NM_001130069.4		c.88A>G	p.Met30Val	missense	Exon 2 of 8	NP_001123541.2	Q8NBJ7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	ENST00000434526.8	TSL:1 MANE Select	c.88A>G	p.Met30Val	missense	Exon 2 of 9	ENSP00000400922.3	Q8NBJ7-1
	SUMF2	ENST00000342190.11	TSL:1	c.88A>G	p.Met30Val	missense	Exon 2 of 8	ENSP00000341938.7	Q8NBJ7-3
	SUMF2	ENST00000395436.7	TSL:1	c.88A>G	p.Met30Val	missense	Exon 2 of 8	ENSP00000378824.3	A8MXB9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461124 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726880

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111796

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.88	D
Eigen	Benign	0.076
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.80	T
PhyloP100		6.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.027	D
Polyphen		0.11	B
Vest4		0.38
MutPred		0.82		Gain of sheet (P = 0.0344)
MVP		0.50
MPC		0.078
ClinPred		0.95	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=85/15	polymorphism

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: rs1562860017; hg19: chr7-56136195;