chr2-119245728-G-C

Variant names:

• chr2-119245728-G-C
• rs922485689
• NM_182915.3:c.262G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182915.3(STEAP3):​c.262G>C​(p.Glu88Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STEAP3 NM_182915.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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)

ACMG classification

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=0.1754784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.262G>C	p.Glu88Gln	missense_variant	Exon 3 of 6	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.262G>C	p.Glu88Gln	missense_variant	Exon 3 of 6	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.262G>C (p.E88Q) alteration is located in exon 3 (coding exon 2) of the STEAP3 gene. This alteration results from a G to C substitution at nucleotide position 262, causing the glutamic acid (E) at amino acid position 88 to be replaced by a glutamine (Q). 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	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	.;T;.;T
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.00069
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.77	T;.;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	.;L;.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.77	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.082	B;B;P;B
Vest4		0.13
MutPred		0.52		.;Loss of catalytic residue at E78 (P = 0.081);Loss of catalytic residue at E78 (P = 0.081);Loss of catalytic residue at E78 (P = 0.081);
MVP		0.56
MPC		0.17
ClinPred		0.57	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.30
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs922485689; hg19: chr2-120003304; COSMIC: COSV61531034;