chr7-88284046-C-A

Variant names:

• chr7-88284046-C-A
• rs1981529
• NM_024636.4:c.224G>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.224G>T​(p.Gly75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 50 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=0.078437686).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	NM_024636.4	MANE Select	c.224G>T	p.Gly75Val	missense	Exon 2 of 5	NP_078912.2
	STEAP4	NM_001205315.2		c.224G>T	p.Gly75Val	missense	Exon 3 of 6	NP_001192244.1
	STEAP4	NM_001205316.2		c.224G>T	p.Gly75Val	missense	Exon 2 of 4	NP_001192245.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP4	ENST00000380079.9	TSL:1 MANE Select	c.224G>T	p.Gly75Val	missense	Exon 2 of 5	ENSP00000369419.4
	STEAP4	ENST00000301959.9	TSL:1	c.224G>T	p.Gly75Val	missense	Exon 2 of 4	ENSP00000305545.5
	STEAP4	ENST00000414498.1	TSL:2	c.224G>T	p.Gly75Val	missense	Exon 3 of 4	ENSP00000394399.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 118866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.75
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.39		Loss of glycosylation at S74 (P = 0.0359)
MVP		0.39
MPC		0.26
ClinPred		0.10	T
GERP RS		4.8
Varity_R		0.36
gMVP		0.63
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1981529; hg19: chr7-87913361;