2-119246066-C-T

Position:

• chr2-119246066-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.522+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,510,662 control chromosomes in the GnomAD database, including 665,040 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 0.88 (60183 hom., cov: 34)
  • Exomes 𝑓: 0.94 (604857 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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=-0.85).
• 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.522+78C>T		intron_variant		ENST00000393110.7	NP_878919.2
STEAP3-AS1	NR_046721.1	n.1574G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.522+78C>T		intron_variant		1	NM_182915.3	ENSP00000376822
STEAP3-AS1	ENST00000654197.1	n.976G>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134339 AN: 152154 Hom.: 60145 Cov.: 34

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.905

GnomAD4 exome AF: 0.943 AC: 1280691 AN: 1358390 Hom.: 604857 Cov.: 24 AF XY: 0.944 AC XY: 630538 AN XY: 667804

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.959

Gnomad4 ASJ exome AF: 0.943

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.973

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.945

Gnomad4 OTH exome AF: 0.938

GnomAD4 genome AF: 0.883 AC: 134435 AN: 152272 Hom.: 60183 Cov.: 34 AF XY: 0.887 AC XY: 66036 AN XY: 74454

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.906

Alfa AF: 0.930 Hom.: 36184

Bravo AF: 0.873

Asia WGS AF: 0.970 AC: 3375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.69

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: rs838083; hg19: chr2-120003642;