rs10188946

Variant names:

• chr2-119246204-A-G
• rs10188946
• NM_182915.3:c.522+216A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):​c.522+216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 638,856 control chromosomes in the GnomAD database, including 58,239 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 0.37 (11649 hom., cov: 32)
  • Exomes 𝑓: 0.43 (46590 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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.522+216A>G		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.492+216A>G		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.492+216A>G		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.522+216A>G		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.492+216A>G		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.492+216A>G		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56083 AN: 151974 Hom.: 11631 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.427 AC: 207707 AN: 486764 Hom.: 46590 Cov.: 6 AF XY: 0.429 AC XY: 107811 AN XY: 251386

African (AFR) AF: 0.198 AC: 2618 AN: 13196

American (AMR) AF: 0.568 AC: 9803 AN: 17252

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 5816 AN: 13202

East Asian (EAS) AF: 0.673 AC: 19469 AN: 28908

South Asian (SAS) AF: 0.475 AC: 19934 AN: 41970

European-Finnish (FIN) AF: 0.435 AC: 11305 AN: 25988

Middle Eastern (MID) AF: 0.365 AC: 706 AN: 1936

European-Non Finnish (NFE) AF: 0.399 AC: 127000 AN: 317922

Other (OTH) AF: 0.419 AC: 11056 AN: 26390

GnomAD4 genome AF: 0.369 AC: 56113 AN: 152092 Hom.: 11649 Cov.: 32 AF XY: 0.377 AC XY: 28011 AN XY: 74318

African (AFR) AF: 0.198 AC: 8219 AN: 41504

American (AMR) AF: 0.496 AC: 7579 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3470

East Asian (EAS) AF: 0.681 AC: 3520 AN: 5168

South Asian (SAS) AF: 0.483 AC: 2330 AN: 4820

European-Finnish (FIN) AF: 0.445 AC: 4698 AN: 10562

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26841 AN: 67970

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.388 Hom.: 19973

Bravo AF: 0.368

Asia WGS AF: 0.601 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.83
PhyloP100		-0.016
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: rs10188946; hg19: chr2-120003780;