chr2-119254595-G-A

Variant names:

• chr2-119254595-G-A
• rs12711924
• NM_182915.3:c.1051-89G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	NM_182915.3	MANE Select	c.1051-89G>A		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.1021-89G>A		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.1021-89G>A		intron	N/A	NP_060704.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.1051-89G>A		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.1021-89G>A		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.1021-89G>A		intron	N/A	ENSP00000376819.2

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

African (AFR) AF: 0.158 AC: 4961 AN: 31372

American (AMR) AF: 0.583 AC: 25327 AN: 43452

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9380 AN: 24602

East Asian (EAS) AF: 0.662 AC: 25646 AN: 38738

South Asian (SAS) AF: 0.452 AC: 36890 AN: 81626

European-Finnish (FIN) AF: 0.379 AC: 19588 AN: 51716

Middle Eastern (MID) AF: 0.320 AC: 1641 AN: 5122

European-Non Finnish (NFE) AF: 0.340 AC: 346700 AN: 1019668

Other (OTH) AF: 0.371 AC: 20964 AN: 56508

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

African (AFR) AF: 0.163 AC: 6767 AN: 41458

American (AMR) AF: 0.458 AC: 6999 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3468

East Asian (EAS) AF: 0.667 AC: 3424 AN: 5132

South Asian (SAS) AF: 0.457 AC: 2191 AN: 4792

European-Finnish (FIN) AF: 0.387 AC: 4078 AN: 10548

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22669 AN: 67952

Other (OTH) AF: 0.309 AC: 651 AN: 2110

Alfa AF: 0.335 Hom.: 36620

Bravo AF: 0.322

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.67
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12711924; hg19: chr2-120012171;