rs13401854

Positions:

• chr2-119238602-T-C

Variant summary

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

The NM_182915.3(STEAP3):​c.23-6887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,292 control chromosomes in the GnomAD database, including 257 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 0.055 (257 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP3	NM_182915.3	c.23-6887T>C		intron_variant		ENST00000393110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP3	ENST00000393110.7	c.23-6887T>C		intron_variant		1	NM_182915.3
STEAP3	ENST00000393106.6	c.-76-761T>C		intron_variant		1		P1
STEAP3	ENST00000393107.2	c.-8-6887T>C		intron_variant		1		P1
STEAP3	ENST00000409811.5	c.-8-6887T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8354 AN: 152174 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0549 AC: 8358 AN: 152292 Hom.: 257 Cov.: 32 AF XY: 0.0528 AC XY: 3929 AN XY: 74478

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0270

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0552 Hom.: 57

Bravo AF: 0.0572

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.42

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: rs13401854; hg19: chr2-119996178;