Variant 7-90162028-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012449.3(STEAP1):c.712A>G(p.Ile238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

STEAP1
NM_012449.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

STEAP1 (HGNC:11378): (STEAP family member 1) This gene is predominantly expressed in prostate tissue, and is found to be upregulated in multiple cancer cell lines. The gene product is predicted to be a six-transmembrane protein, and was shown to be a cell surface antigen significantly expressed at cell-cell junctions. [provided by RefSeq, Jul 2008]

STEAP1 links:

STEAP1 (HGNC:):

STEAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22499257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP1	NM_012449.3 linkuse as main transcript	c.712A>G	p.Ile238Val	missense_variant	4/5	ENST00000297205.7	NP_036581.1	Q9UHE8
STEAP2-AS1	NR_110029.2 linkuse as main transcript	n.424+47823T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STEAP1	ENST00000297205.7 linkuse as main transcript	c.712A>G	p.Ile238Val	missense_variant	4/5	1	NM_012449.3	ENSP00000297205.2	Q9UHE8
STEAP1	ENST00000475789.1 linkuse as main transcript	n.831A>G		non_coding_transcript_exon_variant	4/4	1
STEAP1	ENST00000412573.1 linkuse as main transcript	n.166A>G		non_coding_transcript_exon_variant	2/4	3		ENSP00000394402.1	H7C0D8
STEAP2-AS1	ENST00000478318.6 linkuse as main transcript	n.424+47823T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Oct 12, 2024

The c.712A>G (p.I238V) alteration is located in exon 4 (coding exon 3) of the STEAP1 gene. This alteration results from a A to G substitution at nucleotide position 712, causing the isoleucine (I) at amino acid position 238 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.64

M_CAP

Benign

0.024

MetaRNN

Benign

0.22

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.81

REVEL

Benign

0.22

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.0020

Vest4

0.24

MutPred

0.60

Gain of catalytic residue at I238 (P = 0.0082);

MVP

0.73

MPC

1.7

ClinPred

0.088

GERP RS

3.1

Varity_R

0.11

gMVP

0.64

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