rs838072

Positions:

• chr2-119257409-A-G
• chr2-119257409-A-T

Variant summary

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

The NM_182915.3(STEAP3):​c.1215+2561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 1,417,668 control chromosomes in the GnomAD database, including 639,100 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 0.95 (69115 hom., cov: 31)
  • Exomes 𝑓: 0.95 (569985 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1215+2561A>G		intron_variant		ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.1215+2561A>G		intron_variant		1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144905 AN: 152118 Hom.: 69058 Cov.: 31

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.942

GnomAD3 exomes AF: 0.957 AC: 53430 AN: 55812 Hom.: 25577 AF XY: 0.957 AC XY: 27861 AN XY: 29098

Gnomad AFR exome AF: 0.965

Gnomad AMR exome AF: 0.974

Gnomad ASJ exome AF: 0.939

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.985

Gnomad FIN exome AF: 0.946

Gnomad NFE exome AF: 0.946

Gnomad OTH exome AF: 0.958

GnomAD4 exome AF: 0.949 AC: 1200952 AN: 1265432 Hom.: 569985 Cov.: 42 AF XY: 0.950 AC XY: 581907 AN XY: 612526

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.939

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.945

Gnomad4 OTH exome AF: 0.956

GnomAD4 genome AF: 0.953 AC: 145019 AN: 152236 Hom.: 69115 Cov.: 31 AF XY: 0.955 AC XY: 71054 AN XY: 74430

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.943

Alfa AF: 0.946 Hom.: 95409

Bravo AF: 0.954

Asia WGS AF: 0.991 AC: 3447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs838072; hg19: chr2-120014985;