rs375709871

Variant summary

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

The NM_005500.3(SAE1):​c.257C>G​(p.Ser86Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S86F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SAE1
NM_005500.3 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.80
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]

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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 rank MANE Protein UniProt
SAE1NM_005500.3 linkc.257C>G p.Ser86Cys missense_variant Exon 3 of 9 ENST00000270225.12 NP_005491.1 Q9UBE0-1A0A024R0R4
SAE1NM_001145713.2 linkc.257C>G p.Ser86Cys missense_variant Exon 3 of 7 NP_001139185.1 Q9UBE0-3
SAE1NM_001145714.2 linkc.257C>G p.Ser86Cys missense_variant Exon 3 of 8 NP_001139186.1 Q9UBE0-2
SAE1NR_027280.2 linkn.437C>G non_coding_transcript_exon_variant Exon 3 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAE1ENST00000270225.12 linkc.257C>G p.Ser86Cys missense_variant Exon 3 of 9 1 NM_005500.3 ENSP00000270225.6 Q9UBE0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.060
T;T;.;.;.;T;T;.
Eigen
Benign
0.16
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.72
T;T;T;T;T;T;T;T
M_CAP
Benign
0.0094
T
MetaRNN
Uncertain
0.48
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.8
.;.;.;L;.;.;L;L
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.2
.;.;.;D;.;.;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0070
.;.;.;D;.;.;D;D
Sift4G
Uncertain
0.025
D;D;D;D;.;T;D;D
Polyphen
0.54
.;.;.;.;.;.;P;.
Vest4
0.40, 0.40, 0.41, 0.39
MutPred
0.61
.;.;.;Loss of disorder (P = 0.0224);.;Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);
MVP
0.25
MPC
0.31
ClinPred
0.85
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.79
gMVP
0.46

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.

Other links and lift over

dbSNP: rs375709871; hg19: chr19-47653505; API