rs838075

Variant names:

• chr2-119255312-C-T
• rs838075
• NM_182915.3:c.1215+464C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):​c.1215+464C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,114 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (356 hom., cov: 31)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1215+464C>T		intron_variant	Intron 5 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.1215+464C>T		intron_variant	Intron 5 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9587 AN: 151996 Hom.: 356 Cov.: 31

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0556

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0630 AC: 9588 AN: 152114 Hom.: 356 Cov.: 31 AF XY: 0.0600 AC XY: 4463 AN XY: 74360

African (AFR) AF: 0.0547 AC: 2268 AN: 41492

American (AMR) AF: 0.0494 AC: 756 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3466

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5172

South Asian (SAS) AF: 0.0339 AC: 163 AN: 4808

European-Finnish (FIN) AF: 0.0406 AC: 429 AN: 10576

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0815 AC: 5540 AN: 67996

Other (OTH) AF: 0.0550 AC: 116 AN: 2108

Alfa AF: 0.0756 Hom.: 596

Bravo AF: 0.0641

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs838075; hg19: chr2-120012888;