2-119229778-G-T

Variant names:

• chr2-119229778-G-T
• rs708672
• NM_182915.3:c.-393-842G>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.-393-842G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 150,944 control chromosomes in the GnomAD database, including 22,182 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 0.54 (22182 hom., cov: 28)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.-393-842G>T		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.-393-842G>T		intron_variant	Intron 1 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-77+5890G>T		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-9+5890G>T		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-9+5890G>T		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81104 AN: 150826 Hom.: 22156 Cov.: 28

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.538 AC: 81173 AN: 150944 Hom.: 22182 Cov.: 28 AF XY: 0.530 AC XY: 39079 AN XY: 73708

African (AFR) AF: 0.584 AC: 23909 AN: 40914

American (AMR) AF: 0.446 AC: 6798 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1856 AN: 3464

East Asian (EAS) AF: 0.347 AC: 1753 AN: 5056

South Asian (SAS) AF: 0.441 AC: 2105 AN: 4774

European-Finnish (FIN) AF: 0.508 AC: 5312 AN: 10466

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37785 AN: 67734

Other (OTH) AF: 0.555 AC: 1165 AN: 2100

Alfa AF: 0.543 Hom.: 12606

Bravo AF: 0.535

Asia WGS AF: 0.379 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.46
PhyloP100		-0.38
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: rs708672; hg19: chr2-119987354;