NM_015411.4:c.28C>G

Variant names:

• chr7-56064339-C-G
• rs771439830
• NM_015411.4:c.28C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015411.4(SUMF2):​c.28C>G​(p.Pro10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,601,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SUMF2 NM_015411.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.04
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08705297).

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.28C>G	p.Pro10Ala	missense	Exon 1 of 9	NP_056226.3	Q8NBJ7-1
	SUMF2	NM_001366648.2		c.28C>G	p.Pro10Ala	missense	Exon 1 of 10	NP_001353577.1	C9J660
	SUMF2	NM_001130069.4		c.28C>G	p.Pro10Ala	missense	Exon 1 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.28C>G	p.Pro10Ala	missense	Exon 1 of 9	ENSP00000400922.3	Q8NBJ7-1
	SUMF2	ENST00000342190.11	TSL:1	c.28C>G	p.Pro10Ala	missense	Exon 1 of 8	ENSP00000341938.7	Q8NBJ7-3
	SUMF2	ENST00000395436.7	TSL:1	c.28C>G	p.Pro10Ala	missense	Exon 1 of 8	ENSP00000378824.3	A8MXB9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000443 AC: 1 AN: 225504 AF XY: 0.00000814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000995

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1449600 Hom.: 0 Cov.: 32 AF XY: 0.00000417 AC XY: 3 AN XY: 720088

African (AFR) AF: 0.00 AC: 0 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 42716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25754

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 84260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106796

Other (OTH) AF: 0.00 AC: 0 AN: 59912

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000827 AC: 1

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	0.064
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.010
DANN	Benign	0.57
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.45	T
PhyloP100		-2.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.27
Sift	Benign	0.17	T
Sift4G	Benign	0.49	T
Polyphen		0.0090	B
Vest4		0.11
MutPred		0.53		Loss of loop (P = 0.0128)
MVP		0.52
MPC		0.047
ClinPred		0.11	T
GERP RS		-6.5
PromoterAI		0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs771439830; hg19: chr7-56132032;