NM_182915.3:c.379C>G

Variant names:

• chr2-119245845-C-G
• rs145640198
• NM_182915.3:c.379C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_182915.3(STEAP3):​c.379C>G​(p.Pro127Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: STEAP3 NM_182915.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.075914055).
• BS2: High AC in GnomAd4 at 19 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.379C>G	p.Pro127Ala	missense	Exon 3 of 6	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.349C>G	p.Pro117Ala	missense	Exon 2 of 5	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.349C>G	p.Pro117Ala	missense	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.379C>G	p.Pro127Ala	missense	Exon 3 of 6	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.349C>G	p.Pro117Ala	missense	Exon 3 of 6	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.349C>G	p.Pro117Ala	missense	Exon 2 of 5	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251350 AF XY: 0.000118

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 167 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 77 AN XY: 727238

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000124 AC: 138 AN: 1112012

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74324

African (AFR) AF: 0.000217 AC: 9 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.000136

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0014
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.16	N
PhyloP100		3.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.067
Sift	Benign	0.17	T
Sift4G	Benign	0.93	T
Polyphen		0.10	B
Vest4		0.15
MVP		0.56
MPC		0.22
ClinPred		0.045	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.36
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs145640198; hg19: chr2-120003421;