rs137931598

Variant names:

• chr7-90161133-T-A
• rs137931598
• NM_012449.3:c.413T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-90161133-T-A
• chr7-90161133-T-C

Variant summary

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

The NM_012449.3(STEAP1):​c.413T>A​(p.Ile138Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I138T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STEAP1 NM_012449.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.948
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.413T>A	p.Ile138Asn	missense	Exon 3 of 5	NP_036581.1	Q9UHE8
	STEAP2-AS1	NR_110029.2		n.424+48718A>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.413T>A	p.Ile138Asn	missense	Exon 3 of 5	ENSP00000297205.2	Q9UHE8
	STEAP1	ENST00000475789.1	TSL:1	n.532T>A		non_coding_transcript_exon	Exon 3 of 4
	STEAP1	ENST00000892309.1		c.413T>A	p.Ile138Asn	missense	Exon 4 of 6	ENSP00000562368.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Uncertain	0.77	D
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.95
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.26
Sift	Benign	0.063	T
Sift4G	Benign	0.18	T
Polyphen		0.11	B
Vest4		0.47
MutPred		0.64		Gain of catalytic residue at I138 (P = 0.0463)
MVP		0.82
MPC		0.20
ClinPred		0.28	T
GERP RS		2.8
Varity_R		0.25
gMVP		0.70
Mutation Taster		=73/27	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: rs137931598; hg19: chr7-89790447;