rs838103

Positions:

• chr2-119227098-C-T

Variant summary

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

The NM_182915.3(STEAP3):​c.-394+3210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,944 control chromosomes in the GnomAD database, including 25,101 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 0.57 (25101 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP3	NM_182915.3	c.-394+3210C>T		intron_variant		ENST00000393110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP3	ENST00000393110.7	c.-394+3210C>T		intron_variant		1	NM_182915.3
STEAP3	ENST00000393106.6	c.-77+3210C>T		intron_variant		1		P1
STEAP3	ENST00000393107.2	c.-9+3210C>T		intron_variant		1		P1
STEAP3	ENST00000409811.5	c.-9+3210C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86426 AN: 151826 Hom.: 25077 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.569 AC: 86498 AN: 151944 Hom.: 25101 Cov.: 32 AF XY: 0.562 AC XY: 41714 AN XY: 74256

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.572

Alfa AF: 0.567 Hom.: 24039

Bravo AF: 0.565

Asia WGS AF: 0.435 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs838103; hg19: chr2-119984674; COSMIC: COSV61528268;