chr2-119254595-G-A

Position:

• chr2-119254595-G-A

Variant summary

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

The NM_182915.3(STEAP3):​c.1051-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,504,736 control chromosomes in the GnomAD database, including 103,439 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 0.32 (8991 hom., cov: 31)
  • Exomes 𝑓: 0.36 (94448 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP3	NM_182915.3	c.1051-89G>A		intron_variant		ENST00000393110.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP3	ENST00000393110.7	c.1051-89G>A		intron_variant		1	NM_182915.3
STEAP3-AS1	ENST00000654197.1	n.112-6233C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48599 AN: 151814 Hom.: 8971 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.363 AC: 491097 AN: 1352804 Hom.: 94448 AF XY: 0.365 AC XY: 245996 AN XY: 673674

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.452

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.320 AC: 48626 AN: 151932 Hom.: 8991 Cov.: 31 AF XY: 0.329 AC XY: 24443 AN XY: 74224

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.309

Alfa AF: 0.338 Hom.: 18000

Bravo AF: 0.322

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.67

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: rs12711924; hg19: chr2-120012171;