rs1714656995

Variant names:

• chr3-150762831-T-A
• rs1714656995
• NM_005067.7:c.19A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-150762831-T-A
• chr3-150762831-T-G

Variant summary

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

The NM_005067.7(SIAH2):​c.19A>T​(p.Thr7Ser) 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. T7P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SIAH2 NM_005067.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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

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=0.110355735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIAH2	NM_005067.7	c.19A>T	p.Thr7Ser	missense_variant	Exon 1 of 2	ENST00000312960.4	NP_005058.3
SIAH2-AS1	NR_187305.1	n.310+424T>A		intron_variant	Intron 2 of 2
SIAH2-AS1	NR_187306.1	n.113+424T>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIAH2	ENST00000312960.4	c.19A>T	p.Thr7Ser	missense_variant	Exon 1 of 2	1	NM_005067.7	ENSP00000322457.3
SIAH2	ENST00000482706.1	c.-99-261A>T		intron_variant	Intron 1 of 2	3		ENSP00000417619.1
SIAH2	ENST00000472885.1	n.338-261A>T		intron_variant	Intron 1 of 1	4
SIAH2-AS1	ENST00000663257.1	n.255+424T>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.0	N
REVEL	Benign	0.033
Sift	Benign	0.37	T
Sift4G	Benign	0.91	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.24		Gain of glycosylation at S2 (P = 0.0075);
MVP		0.39
MPC		0.86
ClinPred		0.12	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.072
gMVP		0.32

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

Other links and lift over

dbSNP: rs1714656995; hg19: chr3-150480618;