chr2-119245845-C-G

Variant summary

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

The NM_182915.3(STEAP3):ā€‹c.379C>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 33)
Exomes š‘“: 0.00011 ( 0 hom. )

Consequence

STEAP3
NM_182915.3 missense

Scores

2
17

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

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
STEAP3NM_182915.3 linkuse as main transcriptc.379C>G p.Pro127Ala missense_variant 3/6 ENST00000393110.7 NP_878919.2
STEAP3-AS1NR_046721.1 linkuse as main transcriptn.1795G>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STEAP3ENST00000393110.7 linkuse as main transcriptc.379C>G p.Pro127Ala missense_variant 3/61 NM_182915.3 ENSP00000376822 Q658P3-2
STEAP3-AS1ENST00000654197.1 linkuse as main transcriptn.1197G>C non_coding_transcript_exon_variant 4/4

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152160
Hom.:
0
Cov.:
33
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:
28
AN:
251350
Hom.:
0
AF XY:
0.000118
AC XY:
16
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.:
0
Cov.:
31
AF XY:
0.000106
AC XY:
77
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:
19
AN:
152160
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
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.:
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

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 submitterclinical testingAmbry GeneticsSep 29, 2022The 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
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
19
DANN
Benign
0.80
DEOGEN2
Benign
0.040
.;T;.;T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.0014
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.87
D;.;D;D
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.076
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.16
.;N;.;N
MutationTaster
Benign
0.95
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.34
T
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
T
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.

Other links and lift over

dbSNP: rs145640198; hg19: chr2-120003421; API