chr2-119245512-G-T

Position:

• chr2-119245512-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182915.3(STEAP3):​c.46G>T​(p.Asp16Tyr) 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. 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: 4.77

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28746063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.46G>T	p.Asp16Tyr	missense_variant	3/6	ENST00000393110.7	NP_878919.2
STEAP3-AS1	NR_046721.1	n.2128C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.46G>T	p.Asp16Tyr	missense_variant	3/6	1	NM_182915.3	ENSP00000376822
STEAP3-AS1	ENST00000654197.1	n.1530C>A		non_coding_transcript_exon_variant	4/4

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.46G>T (p.D16Y) alteration is located in exon 3 (coding exon 2) of the STEAP3 gene. This alteration results from a G to T substitution at nucleotide position 46, causing the aspartic acid (D) at amino acid position 16 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	.;T;.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D;.;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;M;.;M
MutationTaster	Benign	0.98	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.027	D;D;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		0.99	D;D;D;D
Vest4		0.39
MutPred		0.17		.;Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);
MVP		0.37
MPC		0.65
ClinPred		0.91	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.22
gMVP		0.67

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

Other links and lift over

dbSNP: rs772886032; hg19: chr2-120003088;