NM_182915.3:c.282G>A

Variant names:

• chr2-119245748-G-A
• rs144377604
• NM_182915.3:c.282G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_182915.3(STEAP3):​c.282G>A​(p.Pro94Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,614,216 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (7 hom.)
• Consequence: STEAP3 NM_182915.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.67
• Publications: 1 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-AS1 (HGNC:41053): (STEAP3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-119245748-G-A is Benign according to our data. Variant chr2-119245748-G-A is described in ClinVar as Benign. ClinVar VariationId is 767818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.67 with no splicing effect.
• BS2: High AC in GnomAd4 at 536 AD,Unknown gene.

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.282G>A	p.Pro94Pro	synonymous	Exon 3 of 6	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.252G>A	p.Pro84Pro	synonymous	Exon 2 of 5	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.252G>A	p.Pro84Pro	synonymous	Exon 3 of 6	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.282G>A	p.Pro94Pro	synonymous	Exon 3 of 6	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.252G>A	p.Pro84Pro	synonymous	Exon 3 of 6	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.252G>A	p.Pro84Pro	synonymous	Exon 2 of 5	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 535 AN: 152222 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00101 AC: 254 AN: 251160 AF XY: 0.000648

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000400 AC: 585 AN: 1461876 Hom.: 7 Cov.: 31 AF XY: 0.000303 AC XY: 220 AN XY: 727238

African (AFR) AF: 0.0134 AC: 447 AN: 33480

American (AMR) AF: 0.000716 AC: 32 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1112008

Other (OTH) AF: 0.000596 AC: 36 AN: 60396

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152340 Hom.: 3 Cov.: 33 AF XY: 0.00341 AC XY: 254 AN XY: 74494

African (AFR) AF: 0.0125 AC: 518 AN: 41578

American (AMR) AF: 0.000784 AC: 12 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00306 Hom.: 1

Bravo AF: 0.00415

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=99/1	polymorphism

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: rs144377604; hg19: chr2-120003324; COSMIC: COSV61528425;