2-119245579-C-T

Variant names:

• chr2-119245579-C-T
• rs200527547
• NM_182915.3:c.113C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182915.3(STEAP3):​c.113C>T​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. A38D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STEAP3 NM_182915.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062039435).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	NM_182915.3	MANE Select	c.113C>T	p.Ala38Val	missense	Exon 3 of 6	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.83C>T	p.Ala28Val	missense	Exon 2 of 5	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.83C>T	p.Ala28Val	missense	Exon 3 of 6	NP_060704.2	Q658P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.113C>T	p.Ala38Val	missense	Exon 3 of 6	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.83C>T	p.Ala28Val	missense	Exon 3 of 6	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.83C>T	p.Ala28Val	missense	Exon 2 of 5	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251112 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454168 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721534

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105682

Other (OTH) AF: 0.00 AC: 0 AN: 59958

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.39
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.057
Sift	Benign	0.17	T
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.26		Loss of disorder (P = 0.1026)
MVP		0.19
MPC		0.15
ClinPred		0.083	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.031
gMVP		0.41
Mutation Taster		=82/18	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: rs200527547; hg19: chr2-120003155;