Variant 19-47130961-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005500.3(SAE1):c.31A>G(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SAE1
NM_005500.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

SAE1 (HGNC:30660): (SUMO1 activating enzyme subunit 1) Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]

SAE1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17084044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SAE1	NM_005500.3 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/9	ENST00000270225.12
SAE1	NM_001145713.2 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/7
SAE1	NM_001145714.2 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/8
SAE1	NR_027280.2 linkuse as main transcript	n.127A>G		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAE1	ENST00000270225.12 linkuse as main transcript	c.31A>G	p.Ile11Val	missense_variant	1/9	1	NM_005500.3	P1	Q9UBE0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1397650

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689300

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 18, 2023

The c.31A>G (p.I11V) alteration is located in exon 1 (coding exon 1) of the SAE1 gene. This alteration results from a A to G substitution at nucleotide position 31, causing the isoleucine (I) at amino acid position 11 to be replaced by a valine (V). 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

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.073

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

T;T;D;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

L;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.81

N;.;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.010

D;.;D;D

Sift4G

Benign

0.062

T;T;D;T

Polyphen

0.0

.;.;B;.

Vest4

0.37

MutPred

0.26

Loss of glycosylation at S12 (P = 0.2269);Loss of glycosylation at S12 (P = 0.2269);Loss of glycosylation at S12 (P = 0.2269);Loss of glycosylation at S12 (P = 0.2269);

MVP

0.59

MPC

0.16

ClinPred

0.87

GERP RS

4.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.53

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over