chr2-119238126-T-C

Variant names:

• chr2-119238126-T-C
• rs10182241
• NM_182915.3:c.22+7092T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000393110.7(STEAP3):​c.22+7092T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 152,336 control chromosomes in the GnomAD database, including 42 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 0.013 (42 hom., cov: 33)
• Consequence: STEAP3 ENST00000393110.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 1 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 Gene-Disease associations (from GenCC):

• severe congenital hypochromic anemia with ringed sideroblasts

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1952/152336) while in subpopulation AFR AF = 0.0442 (1836/41560). AF 95% confidence interval is 0.0425. There are 42 homozygotes in GnomAd4. There are 917 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1952 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393110.7. 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.22+7092T>C		intron	N/A	NP_878919.2
	STEAP3	NM_001008410.2		c.-8-7363T>C		intron	N/A	NP_001008410.1
	STEAP3	NM_018234.3		c.-76-1237T>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.22+7092T>C		intron	N/A	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.-76-1237T>C		intron	N/A	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.-8-7363T>C		intron	N/A	ENSP00000376819.2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1949 AN: 152218 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00573

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

GnomAD4 genome AF: 0.0128 AC: 1952 AN: 152336 Hom.: 42 Cov.: 33 AF XY: 0.0123 AC XY: 917 AN XY: 74516

African (AFR) AF: 0.0442 AC: 1836 AN: 41560

American (AMR) AF: 0.00484 AC: 74 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68038

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.0125 Hom.: 6

Bravo AF: 0.0145

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs10182241; hg19: chr2-119995702;