NM_024636.4:c.1232A>G

Variant names:

• chr7-88279546-T-C
• rs202193095
• NM_024636.4:c.1232A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024636.4(STEAP4):​c.1232A>G​(p.Asn411Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,976 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N411I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026768178).

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.1232A>G	p.Asn411Ser	missense	Exon 5 of 5	NP_078912.2	Q687X5-1
	STEAP4	NM_001205315.2		c.1232A>G	p.Asn411Ser	missense	Exon 6 of 6	NP_001192244.1	Q687X5-1
	STEAP4	NM_001205316.2		c.704A>G	p.Asn235Ser	missense	Exon 4 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.1232A>G	p.Asn411Ser	missense	Exon 5 of 5	ENSP00000369419.4	Q687X5-1
	STEAP4	ENST00000301959.9	TSL:1	c.704A>G	p.Asn235Ser	missense	Exon 4 of 4	ENSP00000305545.5	Q687X5-2
	STEAP4	ENST00000879105.1		c.1232A>G	p.Asn411Ser	missense	Exon 6 of 6	ENSP00000549164.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249286 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.022
DANN	Benign	0.41
DEOGEN2	Benign	0.000064	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.97	N
PhyloP100		-0.52
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.017
Sift	Benign	0.41	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.22		Gain of disorder (P = 0.0732)
MVP		0.10
MPC		0.16
ClinPred		0.075	T
GERP RS		-11
Varity_R		0.054
gMVP		0.25
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs202193095; hg19: chr7-87908861;