rs13401854

Variant names:

• chr2-119238602-T-C
• rs13401854
• NM_182915.3:c.23-6887T>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.23-6887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,292 control chromosomes in the GnomAD database, including 257 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 0.055 (257 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.23-6887T>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.23-6887T>C		intron_variant	Intron 2 of 5	1	NM_182915.3	ENSP00000376822.2
STEAP3	ENST00000393106.6	c.-76-761T>C		intron_variant	Intron 1 of 5	1		ENSP00000376818.2
STEAP3	ENST00000393107.2	c.-8-6887T>C		intron_variant	Intron 1 of 4	1		ENSP00000376819.2
STEAP3	ENST00000409811.5	c.-8-6887T>C		intron_variant	Intron 1 of 5	1		ENSP00000386510.1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8354 AN: 152174 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0549 AC: 8358 AN: 152292 Hom.: 257 Cov.: 32 AF XY: 0.0528 AC XY: 3929 AN XY: 74478

African (AFR) AF: 0.0769 AC: 3196 AN: 41540

American (AMR) AF: 0.0461 AC: 705 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4824

European-Finnish (FIN) AF: 0.0270 AC: 287 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3737 AN: 68018

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

Alfa AF: 0.0557 Hom.: 61

Bravo AF: 0.0572

Asia WGS AF: 0.0140 AC: 47 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	3.0
DANN	Benign	0.42
PhyloP100		0.041
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: rs13401854; hg19: chr2-119996178;