chr2-119245796-C-A

Variant names:

• chr2-119245796-C-A
• rs587776963
• NM_182915.3:c.330C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_182915.3(STEAP3):​c.330C>A​(p.Cys110*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STEAP3 NM_182915.3 stop_gained
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: -0.979
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-119245796-C-A is Pathogenic according to our data. Variant chr2-119245796-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 50372.Status of the report is no_assertion_criteria_provided, 0 stars.

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.330C>A	p.Cys110*	stop_gained	Exon 3 of 6	NP_878919.2
	STEAP3	NM_001008410.2		c.300C>A	p.Cys100*	stop_gained	Exon 2 of 5	NP_001008410.1
	STEAP3	NM_018234.3		c.300C>A	p.Cys100*	stop_gained	Exon 3 of 6	NP_060704.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.330C>A	p.Cys110*	stop_gained	Exon 3 of 6	ENSP00000376822.2
	STEAP3	ENST00000393106.6	TSL:1	c.300C>A	p.Cys100*	stop_gained	Exon 3 of 6	ENSP00000376818.2
	STEAP3	ENST00000393107.2	TSL:1	c.300C>A	p.Cys100*	stop_gained	Exon 2 of 5	ENSP00000376819.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
1	-	-	Severe congenital hypochromic anemia with ringed sideroblasts (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	26
DANN	Benign	0.96
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.077	N
PhyloP100		-0.98
Vest4		0.42
GERP RS		-8.3
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs587776963; hg19: chr2-120003372;