rs708670

Variant names:

• chr2-119229661-G-A
• rs708670
• NM_182915.3:c.-393-959G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-119229661-G-A
• chr2-119229661-G-T

Variant summary

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

The NM_182915.3(STEAP3):​c.-393-959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,040 control chromosomes in the GnomAD database, including 9,876 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 0.35 (9876 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 10 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 Gene-Disease associations (from GenCC):

• severe congenital hypochromic anemia with ringed sideroblasts

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.-393-959G>A		intron_variant	Intron 1 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.-393-959G>A		intron_variant	Intron 1 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-77+5773G>A		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-9+5773G>A		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-9+5773G>A		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53835 AN: 151924 Hom.: 9866 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.354 AC: 53873 AN: 152040 Hom.: 9876 Cov.: 32 AF XY: 0.348 AC XY: 25865 AN XY: 74330

African (AFR) AF: 0.281 AC: 11669 AN: 41470

American (AMR) AF: 0.313 AC: 4788 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1216 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1807 AN: 5156

South Asian (SAS) AF: 0.261 AC: 1258 AN: 4824

European-Finnish (FIN) AF: 0.355 AC: 3763 AN: 10586

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28356 AN: 67942

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.385 Hom.: 28513

Bravo AF: 0.350

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.78
DANN	Benign	0.42
PhyloP100		-0.72
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: rs708670; hg19: chr2-119987237;