2-119250409-C-T

Variant names:

• chr2-119250409-C-T
• rs12990907
• NM_182915.3:c.1050+2203C>T

Variant summary

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

The NM_182915.3(STEAP3):​c.1050+2203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,296 control chromosomes in the GnomAD database, including 182 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 0.042 (182 hom., cov: 33)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.087 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.1050+2203C>T		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.1020+2203C>T		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.1020+2203C>T		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.1050+2203C>T		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.1020+2203C>T		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.1020+2203C>T		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6392 AN: 152178 Hom.: 182 Cov.: 33

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0420 AC: 6395 AN: 152296 Hom.: 182 Cov.: 33 AF XY: 0.0428 AC XY: 3190 AN XY: 74458

African (AFR) AF: 0.0182 AC: 756 AN: 41558

American (AMR) AF: 0.0234 AC: 358 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3472

East Asian (EAS) AF: 0.00694 AC: 36 AN: 5190

South Asian (SAS) AF: 0.0941 AC: 453 AN: 4812

European-Finnish (FIN) AF: 0.0664 AC: 705 AN: 10620

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0535 AC: 3639 AN: 68020

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0480 Hom.: 229

Bravo AF: 0.0373

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.80
PhyloP100		0.38
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: rs12990907; hg19: chr2-120007985;