2-119254595-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182915.3(STEAP3):​c.1051-89G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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>C		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.1021-89G>C		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.1021-89G>C		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>C		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.1021-89G>C		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.1021-89G>C		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355408 Hom.: 0 AF XY: 0.00000148 AC XY: 1 AN XY: 674888

African (AFR) AF: 0.00 AC: 0 AN: 31412

American (AMR) AF: 0.00 AC: 0 AN: 43500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24646

East Asian (EAS) AF: 0.00 AC: 0 AN: 38752

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021874

Other (OTH) AF: 0.00 AC: 0 AN: 56594

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-1.7

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;