chr7-88284046-C-A

Position:

• chr7-88284046-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000380079.9(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. 15/21 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. G75D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STEAP4 ENST00000380079.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078437686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.224G>T	p.Gly75Val	missense_variant	2/5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.224G>T	p.Gly75Val	missense_variant	3/6		NP_001192244.1
STEAP4	NM_001205316.2	c.224G>T	p.Gly75Val	missense_variant	2/4		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.224G>T	p.Gly75Val	missense_variant	2/5	1	NM_024636.4	ENSP00000369419	P1
	ENST00000628577.2	n.604-8142C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.33	T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.025	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.0020	B;B;B
Vest4		0.17
MutPred		0.39		Loss of glycosylation at S74 (P = 0.0359);Loss of glycosylation at S74 (P = 0.0359);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1981529; hg19: chr7-87913361;