rs34741656

Variant names:

• chr7-88283906-C-T
• rs34741656
• NM_024636.4:c.364G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 35 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: Benign. The variant received -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.

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.364G>A	p.Ala122Thr	missense	Exon 2 of 5	NP_078912.2	Q687X5-1
	STEAP4	NM_001205315.2		c.364G>A	p.Ala122Thr	missense	Exon 3 of 6	NP_001192244.1	Q687X5-1
	STEAP4	NM_001205316.2		c.364G>A	p.Ala122Thr	missense	Exon 2 of 4	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.364G>A	p.Ala122Thr	missense	Exon 2 of 5	ENSP00000369419.4	Q687X5-1
	STEAP4	ENST00000301959.9	TSL:1	c.364G>A	p.Ala122Thr	missense	Exon 2 of 4	ENSP00000305545.5	Q687X5-2
	STEAP4	ENST00000879105.1		c.364G>A	p.Ala122Thr	missense	Exon 3 of 6	ENSP00000549164.1

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

GnomAD2 exomes AF: 0.142 AC: 35340 AN: 249386 AF XY: 0.146

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 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

African (AFR) AF: 0.0576 AC: 1928 AN: 33480

American (AMR) AF: 0.103 AC: 4611 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5312 AN: 26136

East Asian (EAS) AF: 0.00506 AC: 201 AN: 39696

South Asian (SAS) AF: 0.102 AC: 8813 AN: 86256

European-Finnish (FIN) AF: 0.138 AC: 7380 AN: 53414

Middle Eastern (MID) AF: 0.182 AC: 1048 AN: 5768

European-Non Finnish (NFE) AF: 0.198 AC: 220474 AN: 1111962

Other (OTH) AF: 0.166 AC: 10048 AN: 60394

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

African (AFR) AF: 0.0612 AC: 2543 AN: 41540

American (AMR) AF: 0.146 AC: 2230 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5180

South Asian (SAS) AF: 0.0894 AC: 431 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1322 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13552 AN: 67984

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.175 Hom.: 8727

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 v4.9

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
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.94	P
Vest4		0.80
MPC		0.63
ClinPred		0.042	T
GERP RS		5.9
Varity_R		0.37
gMVP		0.49
Mutation Taster		=60/40	polymorphism (auto)

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