Variant 7-56064343-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015411.4(SUMF2):c.32T>G(p.Leu11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,492 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SUMF2
NM_015411.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503

Variant links:

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]

SUMF2 links:

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ACMG classification

Classification made for transcript

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 link	c.32T>G	p.Leu11Arg	missense_variant	1/9	ENST00000434526.8	NP_056226.3	Q8NBJ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF2	ENST00000434526.8 link	c.32T>G	p.Leu11Arg	missense_variant	1/9	1	NM_015411.4	ENSP00000400922.3		Q8NBJ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000440

AC:

AN:

227228

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123836

show subpopulations

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 SAS exome

AF:

0.0000352

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450492

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.89T>G (p.L30R) 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 89, causing the leucine (L) at amino acid position 30 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

0.17

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.27

T;T;T;.;.;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.69

T;T;T;.;T;T;T;T

M_CAP

Uncertain

0.25

MetaRNN

Uncertain

0.52

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.032

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N

REVEL

Uncertain

0.45

Sift

Benign

0.13

T;T;T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T

Polyphen

0.61

P;.;.;P;P;.;.;.

Vest4

0.40

MutPred

0.68

Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);.;.;.;

MVP

0.86

MPC

0.33

ClinPred

0.73

GERP RS

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over