2-119238577-A-T

Variant names:

• chr2-119238577-A-T
• rs838092
• NM_182915.3:c.23-6912A>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.23-6912A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,044 control chromosomes in the GnomAD database, including 10,010 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 0.36 (10010 hom., cov: 33)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.23-6912A>T		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.23-6912A>T		intron_variant	Intron 2 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-76-786A>T		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-8-6912A>T		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-8-6912A>T		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54121 AN: 151926 Hom.: 10001 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.356 AC: 54163 AN: 152044 Hom.: 10010 Cov.: 33 AF XY: 0.350 AC XY: 26017 AN XY: 74324

African (AFR) AF: 0.284 AC: 11787 AN: 41474

American (AMR) AF: 0.315 AC: 4808 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1819 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1241 AN: 4828

European-Finnish (FIN) AF: 0.346 AC: 3651 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28574 AN: 67962

Other (OTH) AF: 0.377 AC: 796 AN: 2114

Alfa AF: 0.253 Hom.: 588

Bravo AF: 0.351

Asia WGS AF: 0.287 AC: 999 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	3.9
DANN	Benign	0.47
PhyloP100		-0.015
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs838092; hg19: chr2-119996153; COSMIC: COSV61528315;