7-88280924-T-C

Variant names:

• chr7-88280924-T-C
• NM_024636.4:c.1140A>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024636.4(STEAP4):​c.1140A>G​(p.Arg380Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: STEAP4 NM_024636.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

Genes affected

STEAP4 (HGNC:21923): (STEAP4 metalloreductase) The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

ENSG00000228113 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=3.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.1140A>G	p.Arg380Arg	synonymous_variant	Exon 4 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.1140A>G	p.Arg380Arg	synonymous_variant	Exon 5 of 6		NP_001192244.1
STEAP4	NM_001205316.2	c.612A>G	p.Arg204Arg	synonymous_variant	Exon 3 of 4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.1140A>G	p.Arg380Arg	synonymous_variant	Exon 4 of 5	1	NM_024636.4	ENSP00000369419.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452206 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.0
DANN	Benign	0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-87910239;