2-119246066-C-T

Variant names:

• chr2-119246066-C-T
• rs838083
• NM_182915.3:c.522+78C>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.522+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,510,662 control chromosomes in the GnomAD database, including 665,040 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 0.88 (60183 hom., cov: 34)
  • Exomes 𝑓: 0.94 (604857 hom.)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.522+78C>T		intron_variant	Intron 3 of 5	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.522+78C>T		intron_variant	Intron 3 of 5	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134339 AN: 152154 Hom.: 60145 Cov.: 34

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.905

GnomAD4 exome AF: 0.943 AC: 1280691 AN: 1358390 Hom.: 604857 Cov.: 24 AF XY: 0.944 AC XY: 630538 AN XY: 667804

African (AFR) AF: 0.698 AC: 21618 AN: 30980

American (AMR) AF: 0.959 AC: 33765 AN: 35218

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 20111 AN: 21324

East Asian (EAS) AF: 1.00 AC: 38795 AN: 38802

South Asian (SAS) AF: 0.973 AC: 71043 AN: 72990

European-Finnish (FIN) AF: 0.969 AC: 35732 AN: 36868

Middle Eastern (MID) AF: 0.919 AC: 4802 AN: 5228

European-Non Finnish (NFE) AF: 0.945 AC: 1001861 AN: 1060490

Other (OTH) AF: 0.938 AC: 52964 AN: 56490

GnomAD4 genome AF: 0.883 AC: 134435 AN: 152272 Hom.: 60183 Cov.: 34 AF XY: 0.887 AC XY: 66036 AN XY: 74454

African (AFR) AF: 0.713 AC: 29609 AN: 41514

American (AMR) AF: 0.934 AC: 14305 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3294 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5182

South Asian (SAS) AF: 0.972 AC: 4685 AN: 4822

European-Finnish (FIN) AF: 0.968 AC: 10283 AN: 10618

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64039 AN: 68038

Other (OTH) AF: 0.906 AC: 1915 AN: 2114

Alfa AF: 0.931 Hom.: 39552

Bravo AF: 0.873

Asia WGS AF: 0.970 AC: 3375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.69
PhyloP100		0.050
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: rs838083; hg19: chr2-120003642;