7-90164531-G-C

Variant names:

• chr7-90164531-G-C
• rs147507198
• NM_012449.3:c.817G>C

Variant summary

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

The NM_012449.3(STEAP1):​c.817G>C​(p.Ala273Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A273T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STEAP1 NM_012449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.03
• Publications: 0 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, 0.748

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012449.3. 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
	STEAP1	NM_012449.3	MANE Select	c.817G>C	p.Ala273Pro	missense	Exon 5 of 5	NP_036581.1	Q9UHE8
	STEAP2-AS1	NR_110029.2		n.424+45320C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1	ENST00000297205.7	TSL:1 MANE Select	c.817G>C	p.Ala273Pro	missense	Exon 5 of 5	ENSP00000297205.2	Q9UHE8
	STEAP1	ENST00000892309.1		c.817G>C	p.Ala273Pro	missense	Exon 6 of 6	ENSP00000562368.1
	STEAP1	ENST00000927746.1		c.817G>C	p.Ala273Pro	missense	Exon 6 of 6	ENSP00000597805.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460818 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726652

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111526

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0061	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.021	D
Polyphen		0.99	D
Vest4		0.73
MutPred		0.64		Loss of helix (P = 0.028)
MVP		0.54
MPC		0.21
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.75
gMVP		0.93
Mutation Taster		=25/75	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: rs147507198; hg19: chr7-89793845;