3-150750021-G-T

Variant names:

• chr3-150750021-G-T
• rs6788895
• NM_005067.7:c.418-7323C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005067.7(SIAH2):​c.418-7323C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,078 control chromosomes in the GnomAD database, including 5,445 homozygotes. 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: 𝑓 0.18 (5445 hom., cov: 32)
• Consequence: SIAH2 NM_005067.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 23 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]

ERICH6-AS1 (HGNC:41205): (ERICH6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAH2	NM_005067.7	MANE Select	c.418-7323C>A		intron	N/A	NP_005058.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIAH2	ENST00000312960.4	TSL:1 MANE Select	c.418-7323C>A		intron	N/A	ENSP00000322457.3
	SIAH2	ENST00000482706.1	TSL:3	c.40-7323C>A		intron	N/A	ENSP00000417619.1
	ERICH6-AS1	ENST00000771356.1		n.205-8154G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27551 AN: 151960 Hom.: 5425 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27624 AN: 152078 Hom.: 5445 Cov.: 32 AF XY: 0.182 AC XY: 13525 AN XY: 74354

African (AFR) AF: 0.480 AC: 19884 AN: 41434

American (AMR) AF: 0.132 AC: 2016 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1922 AN: 5172

South Asian (SAS) AF: 0.167 AC: 805 AN: 4812

European-Finnish (FIN) AF: 0.0391 AC: 414 AN: 10592

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0316 AC: 2151 AN: 67992

Other (OTH) AF: 0.152 AC: 320 AN: 2110

Alfa AF: 0.0797 Hom.: 7234

Bravo AF: 0.203

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0020
DANN	Benign	0.75
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6788895; hg19: chr3-150467808;