2-119253323-C-G

Variant names:

• chr2-119253323-C-G
• rs7596511
• NM_182915.3:c.1051-1361C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):​c.1051-1361C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,184 control chromosomes in the GnomAD database, including 1,389 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 0.083 (1389 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

Genes affected

STEAP3 (HGNC:24592): (STEAP3 metalloreductase) This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

STEAP3-AS1 (HGNC:41053): (STEAP3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1051-1361C>G		intron_variant	Intron 4 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.1051-1361C>G		intron_variant	Intron 4 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12555 AN: 152066 Hom.: 1383 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0826 AC: 12574 AN: 152184 Hom.: 1389 Cov.: 32 AF XY: 0.0811 AC XY: 6031 AN XY: 74394

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.0141

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0163 Hom.: 22

Bravo AF: 0.0932

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.71

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: rs7596511; hg19: chr2-120010899;