Genetic Variant STEAP2:p.Arg163Gln (chr7-90225570-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001244944.2(STEAP2):c.488G>A(p.Arg163Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000303 in 1,584,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R163W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

STEAP2
NM_001244944.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

Publications

3 publications found

Variant links:

Genes affected

STEAP2 (HGNC:17885): (STEAP2 metalloreductase) This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

STEAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2779206).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244944.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP2	NM_001244944.2	MANE Select	c.488G>A	p.Arg163Gln	missense	Exon 3 of 6	NP_001231873.1	Q8NFT2-1
STEAP2	NM_001040665.2		c.488G>A	p.Arg163Gln	missense	Exon 3 of 6	NP_001035755.1	Q8NFT2-1
STEAP2	NM_152999.4		c.488G>A	p.Arg163Gln	missense	Exon 2 of 5	NP_694544.2	Q8NFT2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP2	ENST00000394621.7	TSL:1 MANE Select	c.488G>A	p.Arg163Gln	missense	Exon 3 of 6	ENSP00000378119.2	Q8NFT2-1
STEAP2	ENST00000287908.7	TSL:1	c.488G>A	p.Arg163Gln	missense	Exon 2 of 5	ENSP00000287908.3	Q8NFT2-1
STEAP2	ENST00000394622.6	TSL:1	c.488G>A	p.Arg163Gln	missense	Exon 3 of 6	ENSP00000378120.2	Q8NFT2-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000314

AC:

AN:

222606

AF XY:

0.0000332

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000384

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000202

AC:

AN:

1432306

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

710656

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

32038

American (AMR)

AF:

0.00

AC:

AN:

38464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24210

East Asian (EAS)

AF:

0.00

AC:

AN:

39486

South Asian (SAS)

AF:

0.00

AC:

AN:

80500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

1100456

Other (OTH)

AF:

0.0000338

AC:

AN:

59100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41518

American (AMR)

AF:

0.000393

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000918

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.014

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

PhyloP100

5.6

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.25

Sift

Uncertain

0.0090

Sift4G

Benign

0.11

Polyphen

0.97

Vest4

0.48

MVP

0.31

MPC

0.12

ClinPred

0.75

GERP RS

5.6

Varity_R

0.39

gMVP

0.76

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over