rs138657061

Variant names:

• chr2-119245683-C-A
• rs138657061
• NM_182915.3:c.217C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-119245683-C-A
• chr2-119245683-C-G
• chr2-119245683-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182915.3(STEAP3):​c.217C>A​(p.Arg73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,414 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STEAP3 NM_182915.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.217C>A	p.Arg73Ser	missense_variant	Exon 3 of 6	ENST00000393110.7	NP_878919.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP3	ENST00000393110.7	c.217C>A	p.Arg73Ser	missense_variant	Exon 3 of 6	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461414 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726926

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.4	.;L;.;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.51	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.43	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.97	D;P;D;P
Vest4		0.62
MutPred		0.57		.;Loss of methylation at R63 (P = 0.0325);Loss of methylation at R63 (P = 0.0325);Loss of methylation at R63 (P = 0.0325);
MVP		0.55
MPC		0.71
ClinPred		0.86	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.53
gMVP		0.79

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: rs138657061; hg19: chr2-120003259;