Variant chr3-150762650-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005067.7(SIAH2):c.200T>G(p.Val67Gly) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 1.68

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 (HGNC:):

SIAH2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10433853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIAH2	NM_005067.7 linkuse as main transcript	c.200T>G	p.Val67Gly	missense_variant	1/2	ENST00000312960.4	NP_005058.3	O43255
SIAH2-AS1	NR_187305.1 linkuse as main transcript	n.310+243A>C		intron_variant
SIAH2-AS1	NR_187306.1 linkuse as main transcript	n.113+243A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIAH2	ENST00000312960.4 linkuse as main transcript	c.200T>G	p.Val67Gly	missense_variant	1/2	1	NM_005067.7	ENSP00000322457.3	O43255
SIAH2	ENST00000482706.1 linkuse as main transcript	c.-99-80T>G		intron_variant		3		ENSP00000417619.1	C9J9D7
SIAH2	ENST00000472885.1 linkuse as main transcript	n.338-80T>G		intron_variant		4
SIAH2-AS1	ENST00000663257.1 linkuse as main transcript	n.255+243A>C		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1393374

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691498

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.:

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

Aug 04, 2024

The c.200T>G (p.V67G) alteration is located in exon 1 (coding exon 1) of the SIAH2 gene. This alteration results from a T to G substitution at nucleotide position 200, causing the valine (V) at amino acid position 67 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.091

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.38

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.030

REVEL

Benign

0.037

Sift

Benign

0.37

Sift4G

Benign

0.42

Polyphen

0.013

Vest4

0.21

MutPred

0.25

Gain of relative solvent accessibility (P = 0.005);

MVP

0.36

MPC

1.2

ClinPred

0.17

GERP RS

3.1

Varity_R

0.055

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over