7-56064334-T-G

Variant names:

• chr7-56064334-T-G
• NM_015411.4:c.23T>G

Variant summary

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

The NM_015411.4(SUMF2):​c.23T>G​(p.Leu8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUMF2 NM_015411.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.239
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.23T>G	p.Leu8Arg	missense	Exon 1 of 9	NP_056226.3	Q8NBJ7-1
	SUMF2	NM_001366648.2		c.23T>G	p.Leu8Arg	missense	Exon 1 of 10	NP_001353577.1	C9J660
	SUMF2	NM_001130069.4		c.23T>G	p.Leu8Arg	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.23T>G	p.Leu8Arg	missense	Exon 1 of 9	ENSP00000400922.3	Q8NBJ7-1
	SUMF2	ENST00000342190.11	TSL:1	c.23T>G	p.Leu8Arg	missense	Exon 1 of 8	ENSP00000341938.7	Q8NBJ7-3
	SUMF2	ENST00000395436.7	TSL:1	c.23T>G	p.Leu8Arg	missense	Exon 1 of 8	ENSP00000378824.3	A8MXB9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	16
DANN	Benign	0.44
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.040	D
PhyloP100		-0.24
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.42
Sift	Benign	0.31	T
Sift4G	Benign	0.082	T
Polyphen		0.77	P
Vest4		0.49
MutPred		0.68		Gain of MoRF binding (P = 0.0153)
MVP		0.86
MPC		0.33
ClinPred		0.64	D
GERP RS		0.69
PromoterAI		-0.064	Neutral
Mutation Taster		=98/2	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

hg19: chr7-56132027;