2-119251951-C-T

Variant names:

• chr2-119251951-C-T
• rs1867856
• NM_182915.3:c.1051-2733C>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.1051-2733C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,056 control chromosomes in the GnomAD database, including 8,895 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 0.31 (8895 hom., cov: 32)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1051-2733C>T		intron_variant	Intron 4 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.1051-2733C>T		intron_variant	Intron 4 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47479 AN: 151936 Hom.: 8878 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.312 AC: 47505 AN: 152056 Hom.: 8895 Cov.: 32 AF XY: 0.322 AC XY: 23934 AN XY: 74328

African (AFR) AF: 0.131 AC: 5423 AN: 41490

American (AMR) AF: 0.456 AC: 6963 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3468

East Asian (EAS) AF: 0.669 AC: 3457 AN: 5170

South Asian (SAS) AF: 0.465 AC: 2237 AN: 4812

European-Finnish (FIN) AF: 0.383 AC: 4041 AN: 10556

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

European-Non Finnish (NFE) AF: 0.337 AC: 22892 AN: 67978

Other (OTH) AF: 0.309 AC: 654 AN: 2114

Alfa AF: 0.333 Hom.: 1535

Bravo AF: 0.313

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.030
DANN	Benign	0.80
PhyloP100		-2.3
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: rs1867856; hg19: chr2-120009527;