rs769999877

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_005067.7(SIAH2):​c.47G>C​(p.Ser16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. S16N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SIAH2
NM_005067.7 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.744
Variant links:
Genes affected
SIAH2 (HGNC:10858): (siah E3 ubiquitin protein ligase 2) This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. [provided by RefSeq, Jul 2008]
SIAH2-AS1 (HGNC:40526): (SIAH2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a mutagenesis_site Strongly reduced phosphorylation by DYRK2; when associated with A-26; A-28; A-68 and A-119. (size 0) in uniprot entity SIAH2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.083726704).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIAH2NM_005067.7 linkc.47G>C p.Ser16Thr missense_variant Exon 1 of 2 ENST00000312960.4 NP_005058.3 O43255
SIAH2-AS1NR_187305.1 linkn.310+396C>G intron_variant Intron 2 of 2
SIAH2-AS1NR_187306.1 linkn.113+396C>G intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIAH2ENST00000312960.4 linkc.47G>C p.Ser16Thr missense_variant Exon 1 of 2 1 NM_005067.7 ENSP00000322457.3 O43255
SIAH2ENST00000482706.1 linkc.-99-233G>C intron_variant Intron 1 of 2 3 ENSP00000417619.1 C9J9D7
SIAH2ENST00000472885.1 linkn.338-233G>C intron_variant Intron 1 of 1 4
SIAH2-AS1ENST00000663257.1 linkn.255+396C>G intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1077336
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
515174
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.0000196
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.32
T
M_CAP
Pathogenic
0.34
D
MetaRNN
Benign
0.084
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.041
Sift
Benign
0.66
T
Sift4G
Benign
0.57
T
Polyphen
0.0050
B
Vest4
0.086
MutPred
0.18
Loss of glycosylation at P20 (P = 0.0018);
MVP
0.28
MPC
0.88
ClinPred
0.34
T
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.077
gMVP
0.35

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: rs769999877; hg19: chr3-150480590; API