2-119250409-C-T

Position:

• chr2-119250409-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.1050+2203C>T		intron_variant		ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.1050+2203C>T		intron_variant		1	NM_182915.3	ENSP00000376822
STEAP3-AS1	ENST00000654197.1	n.112-2047G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.00694

Gnomad4 SAS AF: 0.0941

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0481 Hom.: 180

Bravo AF: 0.0373

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs12990907; hg19: chr2-120007985;