rs708675

Variant names:

• chr2-119251781-T-C
• rs708675
• NM_182915.3:c.1051-2903T>C

Variant summary

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

The NM_182915.3(STEAP3):​c.1051-2903T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,912 control chromosomes in the GnomAD database, including 28,771 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 0.61 (28771 hom., cov: 31)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1051-2903T>C		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.1051-2903T>C		intron_variant	Intron 4 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92092 AN: 151794 Hom.: 28747 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.607 AC: 92147 AN: 151912 Hom.: 28771 Cov.: 31 AF XY: 0.599 AC XY: 44463 AN XY: 74228

African (AFR) AF: 0.719 AC: 29763 AN: 41410

American (AMR) AF: 0.494 AC: 7546 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1705 AN: 5148

South Asian (SAS) AF: 0.451 AC: 2168 AN: 4810

European-Finnish (FIN) AF: 0.566 AC: 5979 AN: 10556

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41172 AN: 67942

Other (OTH) AF: 0.615 AC: 1301 AN: 2114

Alfa AF: 0.596 Hom.: 4791

Bravo AF: 0.605

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		0.22
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: rs708675; hg19: chr2-120009357;