rs34741656

Positions:

• chr7-88283906-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024636.4(STEAP4):​c.364G>A​(p.Ala122Thr) variant causes a missense change. The variant allele was found at a frequency of 0.174 in 1,613,986 control chromosomes in the GnomAD database, including 26,838 homozygotes. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1820 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25018 hom.)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018156767).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STEAP4	NM_024636.4	c.364G>A	p.Ala122Thr	missense_variant	2/5	ENST00000380079.9
STEAP4	NM_001205315.2	c.364G>A	p.Ala122Thr	missense_variant	3/6
STEAP4	NM_001205316.2	c.364G>A	p.Ala122Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STEAP4	ENST00000380079.9	c.364G>A	p.Ala122Thr	missense_variant	2/5	1	NM_024636.4	P1
	ENST00000628577.2	n.604-8282C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21546 AN: 152052 Hom.: 1820 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.142 AC: 35340 AN: 249386 Hom.: 3081 AF XY: 0.146 AC XY: 19803 AN XY: 135296

Gnomad AFR exome AF: 0.0583

Gnomad AMR exome AF: 0.0989

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.00206

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.178 AC: 259815 AN: 1461814 Hom.: 25018 Cov.: 31 AF XY: 0.176 AC XY: 128300 AN XY: 727216

Gnomad4 AFR exome AF: 0.0576

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.00506

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.142 AC: 21540 AN: 152172 Hom.: 1820 Cov.: 32 AF XY: 0.136 AC XY: 10138 AN XY: 74416

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0894

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.179

Alfa AF: 0.181 Hom.: 4317

Bravo AF: 0.140

TwinsUK AF: 0.202 AC: 748

ALSPAC AF: 0.194 AC: 748

ESP6500AA AF: 0.0604 AC: 228

ESP6500EA AF: 0.200 AC: 1649

ExAC AF: 0.143 AC: 17275

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;D
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;M;.
MutationTaster	Benign	0.0055	P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.94	P;D;P
Vest4		0.80
MPC		0.63
ClinPred		0.042	T
GERP RS		5.9
Varity_R		0.37
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs34741656; hg19: chr7-87913221; COSMIC: COSV57331645;