NM_012449.3:c.507C>G

Variant names:

• chr7-90161227-C-G
• rs2888782
• NM_012449.3:c.507C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012449.3(STEAP1):​c.507C>G​(p.Phe169Leu) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STEAP1 NM_012449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 4 publications found

Genes affected

STEAP1 (HGNC:11378): (STEAP family member 1) This gene is predominantly expressed in prostate tissue, and is found to be upregulated in multiple cancer cell lines. The gene product is predicted to be a six-transmembrane protein, and was shown to be a cell surface antigen significantly expressed at cell-cell junctions. [provided by RefSeq, Jul 2008]

STEAP2-AS1 (HGNC:40820): (STEAP2 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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1	NM_012449.3	c.507C>G	p.Phe169Leu	missense_variant	Exon 3 of 5	ENST00000297205.7	NP_036581.1
STEAP2-AS1	NR_110029.2	n.424+48624G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP1	ENST00000297205.7	c.507C>G	p.Phe169Leu	missense_variant	Exon 3 of 5	1	NM_012449.3	ENSP00000297205.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.66	N
PhyloP100		1.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.52
Sift	Benign	0.58	T
Sift4G	Benign	0.48	T
Polyphen		0.12	B
Vest4		0.79
MutPred		0.25		Loss of stability (P = 0.1487);
MVP		0.64
MPC		0.062
ClinPred		0.24	T
GERP RS		3.4
Varity_R		0.47
gMVP		0.84
Mutation Taster		=27/73	disease causing

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: rs2888782; hg19: chr7-89790541;