chr19-47143522-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2
The NM_005500.3(SAE1):c.127G>A(p.Gly43Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,613,986 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00024 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 12 hom. )
Consequence
SAE1
NM_005500.3 missense
NM_005500.3 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 9.46
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 Benign. Variant got -9 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.044219077).
BP6
?
Variant 19-47143522-G-A is Benign according to our data. Variant chr19-47143522-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650142.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SAE1 | NM_005500.3 | c.127G>A | p.Gly43Ser | missense_variant | 2/9 | ENST00000270225.12 | |
SAE1 | NM_001145713.2 | c.127G>A | p.Gly43Ser | missense_variant | 2/7 | ||
SAE1 | NM_001145714.2 | c.127G>A | p.Gly43Ser | missense_variant | 2/8 | ||
SAE1 | NR_027280.2 | n.307G>A | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SAE1 | ENST00000270225.12 | c.127G>A | p.Gly43Ser | missense_variant | 2/9 | 1 | NM_005500.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152024Hom.: 2 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00109 AC: 274AN: 251484Hom.: 4 AF XY: 0.00141 AC XY: 192AN XY: 135918
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GnomAD4 exome AF: 0.000559 AC: 817AN: 1461844Hom.: 12 Cov.: 30 AF XY: 0.000782 AC XY: 569AN XY: 727226
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GnomAD4 genome ? AF: 0.000237 AC: 36AN: 152142Hom.: 2 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | SAE1: PP3, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.;D;D
REVEL
Pathogenic
Sift
Uncertain
D;.;.;D;D
Sift4G
Uncertain
T;.;D;D;T
Polyphen
1.0
.;.;.;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.1186);.;Gain of MoRF binding (P = 0.1186);Gain of MoRF binding (P = 0.1186);Gain of MoRF binding (P = 0.1186);
MVP
MPC
0.72
ClinPred
T
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