2-119245683-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_182915.3(STEAP3):​c.217C>G​(p.Arg73Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R73C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP3	NM_182915.3	c.217C>G	p.Arg73Gly	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>G	p.Arg73Gly	missense_variant	Exon 3 of 6	1	NM_182915.3	ENSP00000376822.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251170 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461414 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.6	.;M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.97	D;B;D;B
Vest4		0.67
MutPred		0.58		.;Loss of MoRF binding (P = 0.0278);Loss of MoRF binding (P = 0.0278);Loss of MoRF binding (P = 0.0278);
MVP		0.61
MPC		0.76
ClinPred		0.92	D
GERP RS		3.0
Varity_R		0.58
gMVP		0.78

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;