Genetic Variant SIAH2:p.Pro14His (chr3-150762809-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005067.7(SIAH2):c.41C>A(p.Pro14His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SIAH2
NM_005067.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

Publications

0 publications found

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 links:

SIAH2-AS1 (HGNC:40526): (SIAH2 antisense RNA 1)

SIAH2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22219583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005067.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SIAH2	NM_005067.7	MANE Select	c.41C>A	p.Pro14His	missense	Exon 1 of 2	NP_005058.3
SIAH2-AS1	NR_187305.1		n.310+402G>T		intron	N/A
SIAH2-AS1	NR_187306.1		n.113+402G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIAH2	ENST00000312960.4	TSL:1 MANE Select	c.41C>A	p.Pro14His	missense	Exon 1 of 2	ENSP00000322457.3	O43255
SIAH2	ENST00000936558.1		c.41C>A	p.Pro14His	missense	Exon 1 of 3	ENSP00000606617.1
SIAH2	ENST00000482706.1	TSL:3	c.-99-239C>A		intron	N/A	ENSP00000417619.1	C9J9D7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1077554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

515006

African (AFR)

AF:

0.00

AC:

AN:

21970

American (AMR)

AF:

0.00

AC:

AN:

14298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11678

East Asian (EAS)

AF:

0.00

AC:

AN:

23464

South Asian (SAS)

AF:

0.00

AC:

AN:

24472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

904152

Other (OTH)

AF:

0.00

AC:

AN:

40094

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.69

PhyloP100

3.7

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.36

REVEL

Benign

0.088

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.056

Polyphen

0.085

Vest4

0.14

MutPred

0.23

Loss of glycosylation at P19 (P = 0.0088)

MVP

0.38

MPC

1.1

ClinPred

0.49

GERP RS

3.2

PromoterAI

0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.45

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over