rs838079

Variant names:

• chr2-119250136-G-A
• rs838079
• NM_182915.3:c.1050+1930G>A

Variant summary

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

The NM_182915.3(STEAP3):​c.1050+1930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,210 control chromosomes in the GnomAD database, including 2,410 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 0.14 (2410 hom., cov: 33)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1050+1930G>A		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.1050+1930G>A		intron_variant	Intron 4 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21021 AN: 152092 Hom.: 2406 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.138 AC: 21048 AN: 152210 Hom.: 2410 Cov.: 33 AF XY: 0.133 AC XY: 9898 AN XY: 74440

African (AFR) AF: 0.317 AC: 13141 AN: 41506

American (AMR) AF: 0.0727 AC: 1113 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 246 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4826

European-Finnish (FIN) AF: 0.0407 AC: 431 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5623 AN: 68004

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.147 Hom.: 385

Bravo AF: 0.149

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.60
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs838079; hg19: chr2-120007712;