7-90161146-T-C

Variant names:

• chr7-90161146-T-C
• rs774801733
• NM_012449.3:c.426T>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012449.3(STEAP1):​c.426T>C​(p.His142His) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-0.065 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1	NM_012449.3	c.426T>C	p.His142His	synonymous_variant	Exon 3 of 5	ENST00000297205.7	NP_036581.1
STEAP2-AS1	NR_110029.2	n.424+48705A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP1	ENST00000297205.7	c.426T>C	p.His142His	synonymous_variant	Exon 3 of 5	1	NM_012449.3	ENSP00000297205.2
STEAP1	ENST00000475789.1	n.545T>C		non_coding_transcript_exon_variant	Exon 3 of 4	1
STEAP2-AS1	ENST00000478318.6	n.424+48705A>G		intron_variant	Intron 2 of 2	3
STEAP1	ENST00000412573.1	n.-121T>C		upstream_gene_variant		3		ENSP00000394402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.8
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs774801733; hg19: chr7-89790460;