3-150762720-C-G

Variant names:

• chr3-150762720-C-G
• rs1392113961
• NM_005067.7:c.130G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005067.7(SIAH2):​c.130G>C​(p.Gly44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G44S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: SIAH2 NM_005067.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

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)

ACMG classification

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=0.2537269).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAH2	NM_005067.7	MANE Select	c.130G>C	p.Gly44Arg	missense	Exon 1 of 2	NP_005058.3
	SIAH2-AS1	NR_187305.1		n.310+313C>G		intron	N/A
	SIAH2-AS1	NR_187306.1		n.113+313C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAH2	ENST00000312960.4	TSL:1 MANE Select	c.130G>C	p.Gly44Arg	missense	Exon 1 of 2	ENSP00000322457.3	O43255
	SIAH2	ENST00000936558.1		c.130G>C	p.Gly44Arg	missense	Exon 1 of 3	ENSP00000606617.1
	SIAH2	ENST00000482706.1	TSL:3	c.-99-150G>C		intron	N/A	ENSP00000417619.1	C9J9D7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049340 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 499972

African (AFR) AF: 0.00 AC: 0 AN: 20710

American (AMR) AF: 0.00 AC: 0 AN: 6508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11460

East Asian (EAS) AF: 0.00 AC: 0 AN: 21210

South Asian (SAS) AF: 0.00 AC: 0 AN: 19526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2720

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 895230

Other (OTH) AF: 0.00 AC: 0 AN: 39634

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.12
Sift	Uncertain	0.029	D
Sift4G	Benign	0.33	T
Polyphen		0.74	P
Vest4		0.17
MutPred		0.28		Loss of glycosylation at P43 (P = 0.0363)
MVP		0.37
MPC		1.1
ClinPred		0.68	D
GERP RS		3.4
PromoterAI		-0.061	Neutral
Varity_R		0.12
gMVP		0.41
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1392113961; hg19: chr3-150480507;