19-47150323-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005500.3(SAE1):c.332A>G(p.Asp111Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SAE1
NM_005500.3 missense
NM_005500.3 missense
Scores
8
3
4
Clinical Significance
Conservation
PhyloP100: 8.83
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.83
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SAE1 | NM_005500.3 | c.332A>G | p.Asp111Gly | missense_variant | 3/9 | ENST00000270225.12 | |
SAE1 | NM_001145713.2 | c.332A>G | p.Asp111Gly | missense_variant | 3/7 | ||
SAE1 | NM_001145714.2 | c.332A>G | p.Asp111Gly | missense_variant | 3/8 | ||
SAE1 | NR_027280.2 | n.512A>G | non_coding_transcript_exon_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAE1 | ENST00000270225.12 | c.332A>G | p.Asp111Gly | missense_variant | 3/9 | 1 | NM_005500.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461322Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726964
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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 | Dec 13, 2023 | The c.332A>G (p.D111G) alteration is located in exon 3 (coding exon 3) of the SAE1 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the aspartic acid (D) at amino acid position 111 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;.;T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D;D;.;D;D;D;D
Polyphen
0.96
.;.;.;.;.;.;.;D;.
Vest4
0.84, 0.84, 0.83, 0.83
MutPred
0.47
.;.;.;Loss of ubiquitination at K109 (P = 0.0613);.;Loss of ubiquitination at K109 (P = 0.0613);.;Loss of ubiquitination at K109 (P = 0.0613);Loss of ubiquitination at K109 (P = 0.0613);
MVP
MPC
0.86
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at