chr2-119227157-G-A

Variant names:

• chr2-119227157-G-A
• rs838102
• NM_182915.3:c.-394+3269G>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.-394+3269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,952 control chromosomes in the GnomAD database, including 9,482 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 0.34 (9482 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 15 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, NO_KNOWN Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, 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 (NFE) allele frequency at 95% confidence interval = 0.417 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	NM_182915.3	MANE Select	c.-394+3269G>A		intron	N/A	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.-9+3269G>A		intron	N/A	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.-77+3269G>A		intron	N/A	NP_060704.2	Q658P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.-394+3269G>A		intron	N/A	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.-77+3269G>A		intron	N/A	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.-9+3269G>A		intron	N/A	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52270 AN: 151834 Hom.: 9477 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.344 AC: 52300 AN: 151952 Hom.: 9482 Cov.: 32 AF XY: 0.337 AC XY: 25064 AN XY: 74276

African (AFR) AF: 0.235 AC: 9719 AN: 41420

American (AMR) AF: 0.316 AC: 4828 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1841 AN: 5162

South Asian (SAS) AF: 0.251 AC: 1204 AN: 4796

European-Finnish (FIN) AF: 0.355 AC: 3744 AN: 10556

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28591 AN: 67966

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.394 Hom.: 20763

Bravo AF: 0.338

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.58
PhyloP100		-0.69
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs838102;

hg19: chr2-119984733;

COSMIC: COSV61528276;