rs12465926

Variant names:

• chr2-119234997-T-C
• rs12465926
• NM_182915.3:c.22+3963T>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.22+3963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,306 control chromosomes in the GnomAD database, including 679 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 0.078 (679 hom., cov: 33)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.22+3963T>C		intron_variant	Intron 2 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.22+3963T>C		intron_variant	Intron 2 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-76-4366T>C		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-8-10492T>C		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-8-10492T>C		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11881 AN: 152188 Hom.: 678 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.0781 AC: 11888 AN: 152306 Hom.: 679 Cov.: 33 AF XY: 0.0763 AC XY: 5684 AN XY: 74478

African (AFR) AF: 0.157 AC: 6519 AN: 41538

American (AMR) AF: 0.0595 AC: 910 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4832

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10624

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0478 AC: 3252 AN: 68032

Other (OTH) AF: 0.0891 AC: 188 AN: 2110

Alfa AF: 0.0717 Hom.: 112

Bravo AF: 0.0834

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.80
DANN	Benign	0.68
PhyloP100		-0.80
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: rs12465926; hg19: chr2-119992573;