chr3-150762728-G-C

Position:

• chr3-150762728-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005067.7(SIAH2):​c.122C>G​(p.Ala41Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SIAH2 NM_005067.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

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 (HGNC:):

ACMG classification

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=0.16672134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIAH2	NM_005067.7	c.122C>G	p.Ala41Gly	missense_variant	1/2	ENST00000312960.4	NP_005058.3
SIAH2-AS1	NR_187305.1	n.310+321G>C		intron_variant
SIAH2-AS1	NR_187306.1	n.113+321G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIAH2	ENST00000312960.4	c.122C>G	p.Ala41Gly	missense_variant	1/2	1	NM_005067.7	ENSP00000322457.3
SIAH2	ENST00000482706.1	c.-99-158C>G		intron_variant		3		ENSP00000417619.1
SIAH2	ENST00000472885.1	n.338-158C>G		intron_variant		4
SIAH2-AS1	ENST00000663257.1	n.255+321G>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

The c.122C>G (p.A41G) alteration is located in exon 1 (coding exon 1) of the SIAH2 gene. This alteration results from a C to G substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 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	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.033
Sift	Benign	0.41	T
Sift4G	Benign	0.41	T
Polyphen		0.16	B
Vest4		0.068
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.27
MPC		0.96
ClinPred		0.35	T
GERP RS		3.5
Varity_R		0.073
gMVP		0.28

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.

Other links and lift over

hg19: chr3-150480515;