7-56064334-T-G

Position:

• chr7-56064334-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF2	NM_015411.4	c.23T>G	p.Leu8Arg	missense_variant	1/9	ENST00000434526.8	NP_056226.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF2	ENST00000434526.8	c.23T>G	p.Leu8Arg	missense_variant	1/9	1	NM_015411.4	ENSP00000400922.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.80T>G (p.L27R) alteration is located in exon 1 (coding exon 1) of the SUMF2 gene. This alteration results from a T to G substitution at nucleotide position 80, causing the leucine (L) at amino acid position 27 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.;.;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.62	T;T;T;.;T;T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.040	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.31	T;T;T;T;D;T;D;T
Sift4G	Benign	0.082	T;T;T;T;D;T;D;T
Polyphen		0.77	P;.;.;D;D;.;.;.
Vest4		0.49
MutPred		0.68		Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);Gain of MoRF binding (P = 0.0153);.;.;.;
MVP		0.86
MPC		0.33
ClinPred		0.64	D
GERP RS		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-56132027;