Variant chr2-119245845-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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. 15/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

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 links:

STEAP3-AS1 (HGNC:41053): (STEAP3 antisense RNA 1)

STEAP3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.075914055).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3 linkuse as main transcript	c.379C>G	p.Pro127Ala	missense_variant	3/6	ENST00000393110.7	NP_878919.2
STEAP3-AS1	NR_046721.1 linkuse as main transcript	n.1795G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7 linkuse as main transcript	c.379C>G	p.Pro127Ala	missense_variant	3/6	1	NM_182915.3	ENSP00000376822		Q658P3-2
STEAP3-AS1	ENST00000654197.1 linkuse as main transcript	n.1197G>C		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251350

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135858

show subpopulations

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 SAS exome

AF:

0.0000327

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.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000125

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.379C>G (p.P127A) alteration is located in exon 3 (coding exon 2) of the STEAP3 gene. This alteration results from a C to G substitution at nucleotide position 379, causing the proline (P) at amino acid position 127 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.040

.;T;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.0014

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.87

D;.;D;D

M_CAP

Benign

0.0092

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.16

.;N;.;N

MutationTaster

Benign

0.95

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.010

N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.93

T;T;T;T

Polyphen

0.10

B;B;B;B

Vest4

0.15

MVP

0.56

MPC

0.22

ClinPred

0.045

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over