rs838074

chr2-119255688-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):c.1215+840T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 151,916 control chromosomes in the GnomAD database, including 343 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 0.061 (343 hom., cov: 31)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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/exons	MANE	UniProt
STEAP3	NM_182915.3	c.1215+840T>A		intron_variant		ENST00000393110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP3	ENST00000393110.7	c.1215+840T>A		intron_variant		1	NM_182915.3
STEAP3-AS1	ENST00000654197.1	n.112-7326A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9308 AN: 151798 Hom.: 343 Cov.: 31

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0613 AC: 9308 AN: 151916 Hom.: 343 Cov.: 31 AF XY: 0.0584 AC XY: 4338 AN XY: 74260

Gnomad4 AFR AF: 0.0486

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0339

Gnomad4 FIN AF: 0.0404

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0679 Hom.: 51

Bravo AF: 0.0622

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.79
Dann	Benign	0.76

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: rs838074; hg19: chr2-120013264;