chr7-88283162-C-A

Variant names:

• chr7-88283162-C-A
• rs772480842
• NM_024636.4:c.463G>T

Variant summary

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

The NM_024636.4(STEAP4):​c.463G>T​(p.Val155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000722 in 1,385,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.467
• Publications: 1 publications found

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]

SRI-AS1 (HGNC:40564): (SRI 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=0.14100832).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024636.4. 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
	STEAP4	NM_024636.4	MANE Select	c.463G>T	p.Val155Leu	missense	Exon 3 of 5	NP_078912.2	Q687X5-1
	STEAP4	NM_001205315.2		c.463G>T	p.Val155Leu	missense	Exon 4 of 6	NP_001192244.1	Q687X5-1
	STEAP4	NM_001205316.2		c.456+652G>T		intron	N/A	NP_001192245.1	Q687X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.463G>T	p.Val155Leu	missense	Exon 3 of 5	ENSP00000369419.4	Q687X5-1
	STEAP4	ENST00000301959.9	TSL:1	c.456+652G>T		intron	N/A	ENSP00000305545.5	Q687X5-2
	STEAP4	ENST00000879105.1		c.463G>T	p.Val155Leu	missense	Exon 4 of 6	ENSP00000549164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000108 AC: 2 AN: 185788 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000636

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000722 AC: 10 AN: 1385434 Hom.: 0 Cov.: 31 AF XY: 0.0000117 AC XY: 8 AN XY: 682172

African (AFR) AF: 0.00 AC: 0 AN: 30632

American (AMR) AF: 0.00 AC: 0 AN: 30540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39086

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078880

Other (OTH) AF: 0.00 AC: 0 AN: 57160

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000831 AC: 1

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	0.22
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.47
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.034
Sift	Benign	0.27	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.65		Loss of MoRF binding (P = 0.1028)
MVP		0.25
MPC		0.20
ClinPred		0.054	T
GERP RS		3.2
Varity_R		0.29
gMVP		0.49
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs772480842; hg19: chr7-87912477;