Variant rs6542517 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_138637.3(STEAP3):c.1350A>T(p.Gln450His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,498,542 control chromosomes in the GnomAD database, including 1,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.065 ( 808 hom., cov: 32)

Exomes 𝑓: 0.018 ( 832 hom. )

Consequence

STEAP3
NM_138637.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0620

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:):

STEAP3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.162094E-4).

BP6

Variant 2-119257621-A-T is Benign according to our data. Variant chr2-119257621-A-T is described in ClinVar as [Benign]. Clinvar id is 3056077.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3 linkuse as main transcript	c.1215+2773A>T		intron_variant		ENST00000393110.7	NP_878919.2	Q658P3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7 linkuse as main transcript	c.1215+2773A>T		intron_variant		1	NM_182915.3	ENSP00000376822.2		Q658P3-2

Frequencies

GnomAD3 genomes

AF:

0.0652

AC:

9917

AN:

152136

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0385

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0297

AC:

2872

AN:

96554

Hom.:

152

AF XY:

0.0296

AC XY:

1558

AN XY:

52712

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0529

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.00243

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

AF:

0.0184

AC:

24710

AN:

1346288

Hom.:

832

Cov.:

AF XY:

0.0192

AC XY:

12701

AN XY:

662454

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.0000611

Gnomad4 SAS exome

AF:

0.0477

Gnomad4 FIN exome

AF:

0.00383

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0332

GnomAD4 genome

AF:

0.0652

AC:

9925

AN:

152254

Hom.:

808

Cov.:

AF XY:

0.0642

AC XY:

4782

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0384

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0443

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0605

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.0733

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00986

AC:

ExAC

AF:

0.0363

AC:

804

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

STEAP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.0

DANN

Benign

0.84

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.25

MetaRNN

Benign

0.00072

MetaSVM

Benign

-0.91

PROVEAN

Benign

-0.90

REVEL

Benign

0.024

Sift

Pathogenic

0.0

Sift4G

Benign

0.15

Polyphen

0.12

Vest4

0.064

MutPred

0.18

Loss of solvent accessibility (P = 0.1551);

ClinPred

0.0038

GERP RS

-0.40

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

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