STEAP1 p.His47Gln

Variant names:

• chr7-90160861-C-A
• NM_012449.3:c.141C>A
• STEAP1 p.His47Gln

Your query was ambiguous. Multiple possible variants found:

• chr7-90160861-C-A
• chr7-90160861-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012449.3(STEAP1):​c.141C>A​(p.His47Gln) 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 benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STEAP1 NM_012449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072523594).

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.141C>A	p.His47Gln	missense	Exon 3 of 5	NP_036581.1	Q9UHE8
	STEAP2-AS1	NR_110029.2		n.424+48990G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1	ENST00000297205.7	TSL:1 MANE Select	c.141C>A	p.His47Gln	missense	Exon 3 of 5	ENSP00000297205.2	Q9UHE8
	STEAP1	ENST00000475789.1	TSL:1	n.260C>A		non_coding_transcript_exon	Exon 3 of 4
	STEAP1	ENST00000892309.1		c.141C>A	p.His47Gln	missense	Exon 4 of 6	ENSP00000562368.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1383080 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690006

African (AFR) AF: 0.00 AC: 0 AN: 31764

American (AMR) AF: 0.00 AC: 0 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 84662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042334

Other (OTH) AF: 0.00 AC: 0 AN: 57636

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.2
DANN	Benign	0.62
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.080
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.11
Sift	Benign	0.46	T
Sift4G	Benign	0.55	T
Varity_R		0.033
gMVP		0.36
Mutation Taster		=95/5	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-89790175;