2-119228407-C-A

Variant names:

• chr2-119228407-C-A
• rs3769659
• NM_182915.3:c.-393-2213C>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.-393-2213C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,998 control chromosomes in the GnomAD database, including 9,464 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 0.33 (9464 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• 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 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 (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.-393-2213C>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.-393-2213C>A		intron_variant	Intron 1 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-77+4519C>A		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-9+4519C>A		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-9+4519C>A		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49821 AN: 151878 Hom.: 9455 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.328 AC: 49851 AN: 151998 Hom.: 9464 Cov.: 32 AF XY: 0.338 AC XY: 25147 AN XY: 74292

African (AFR) AF: 0.157 AC: 6517 AN: 41520

American (AMR) AF: 0.458 AC: 6992 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1174 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3275 AN: 5120

South Asian (SAS) AF: 0.416 AC: 1998 AN: 4806

European-Finnish (FIN) AF: 0.448 AC: 4740 AN: 10570

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23950 AN: 67944

Other (OTH) AF: 0.323 AC: 679 AN: 2100

Alfa AF: 0.278 Hom.: 3090

Bravo AF: 0.326

Asia WGS AF: 0.533 AC: 1852 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	0.64
DANN	Benign	0.45
PhyloP100		-0.64
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: rs3769659; hg19: chr2-119985983;