chr2-119227098-C-T

Variant names:

• chr2-119227098-C-T
• rs838103
• NM_182915.3:c.-394+3210C>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.-394+3210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,944 control chromosomes in the GnomAD database, including 25,101 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 0.57 (25101 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	NM_182915.3	MANE Select	c.-394+3210C>T		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.-9+3210C>T		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.-77+3210C>T		intron	N/A	NP_060704.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.-394+3210C>T		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.-77+3210C>T		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.-9+3210C>T		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86426 AN: 151826 Hom.: 25077 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.569 AC: 86498 AN: 151944 Hom.: 25101 Cov.: 32 AF XY: 0.562 AC XY: 41714 AN XY: 74256

African (AFR) AF: 0.641 AC: 26576 AN: 41434

American (AMR) AF: 0.457 AC: 6982 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2104 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1880 AN: 5150

South Asian (SAS) AF: 0.519 AC: 2494 AN: 4810

European-Finnish (FIN) AF: 0.530 AC: 5594 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39025 AN: 67942

Other (OTH) AF: 0.572 AC: 1210 AN: 2114

Alfa AF: 0.568 Hom.: 29021

Bravo AF: 0.565

Asia WGS AF: 0.435 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.56
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs838103; hg19: chr2-119984674; COSMIC: COSV61528268;