7-56064368-G-C

Position:

• chr7-56064368-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015411.4(SUMF2):​c.57G>C​(p.Trp19Cys) 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: 2.28

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	UniProt
SUMF2	NM_015411.4	c.57G>C	p.Trp19Cys	missense_variant	1/9	ENST00000434526.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF2	ENST00000434526.8	c.57G>C	p.Trp19Cys	missense_variant	1/9	1	NM_015411.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 04, 2023

The c.114G>C (p.W38C) alteration is located in exon 1 (coding exon 1) of the SUMF2 gene. This alteration results from a G to C substitution at nucleotide position 114, causing the tryptophan (W) at amino acid position 38 to be replaced by a cysteine (C). 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	0.17
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.30	T;T;T;.;.;.;.;.
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.82	T;T;T;.;T;T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationTaster	Benign	0.98	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.024	D;D;D;T;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T;T;T;T
Polyphen		0.99	D;.;.;D;D;.;.;.
Vest4		0.52
MutPred		0.62		Gain of catalytic residue at L39 (P = 0.0135);Gain of catalytic residue at L39 (P = 0.0135);Gain of catalytic residue at L39 (P = 0.0135);Gain of catalytic residue at L39 (P = 0.0135);Gain of catalytic residue at L39 (P = 0.0135);.;.;.;
MVP		0.79
MPC		0.34
ClinPred		0.79	D
GERP RS		3.5

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

LitVar

Other links and lift over

dbSNP: rs1262288764; hg19: chr7-56132061;