2-119232060-C-T

Variant names:

• chr2-119232060-C-T
• rs838095
• NM_182915.3:c.22+1026C>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.22+1026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,972 control chromosomes in the GnomAD database, including 9,715 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 0.35 (9715 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 10 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: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 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.22+1026C>T		intron	N/A	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.-9+8172C>T		intron	N/A	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.-76-7303C>T		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.22+1026C>T		intron	N/A	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.-76-7303C>T		intron	N/A	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.-9+8172C>T		intron	N/A	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53260 AN: 151854 Hom.: 9710 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.351 AC: 53286 AN: 151972 Hom.: 9715 Cov.: 32 AF XY: 0.344 AC XY: 25557 AN XY: 74282

African (AFR) AF: 0.265 AC: 10972 AN: 41456

American (AMR) AF: 0.312 AC: 4770 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1812 AN: 5150

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4814

European-Finnish (FIN) AF: 0.356 AC: 3753 AN: 10550

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28494 AN: 67944

Other (OTH) AF: 0.364 AC: 765 AN: 2102

Alfa AF: 0.396 Hom.: 12974

Bravo AF: 0.345

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.9
DANN	Benign	0.85
PhyloP100		-0.47
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: rs838095; hg19: chr2-119989636; COSMIC: COSV61528307;