chr7-88282910-C-T

Variant names:

• chr7-88282910-C-T
• NM_024636.4:c.715G>A

Variant summary

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

The NM_024636.4(STEAP4):​c.715G>A​(p.Ala239Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STEAP4 NM_024636.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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]

ENSG00000228113 (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=0.10589281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP4	NM_024636.4	c.715G>A	p.Ala239Thr	missense_variant	Exon 3 of 5	ENST00000380079.9	NP_078912.2
STEAP4	NM_001205315.2	c.715G>A	p.Ala239Thr	missense_variant	Exon 4 of 6		NP_001192244.1
STEAP4	NM_001205316.2	c.456+904G>A		intron_variant	Intron 2 of 3		NP_001192245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP4	ENST00000380079.9	c.715G>A	p.Ala239Thr	missense_variant	Exon 3 of 5	1	NM_024636.4	ENSP00000369419.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.715G>A (p.A239T) alteration is located in exon 3 (coding exon 2) of the STEAP4 gene. This alteration results from a G to A substitution at nucleotide position 715, causing the alanine (A) at amino acid position 239 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.049	D;T
Polyphen		0.0020	B;B
Vest4		0.28
MutPred		0.58		Gain of glycosylation at A239 (P = 0.0271);Gain of glycosylation at A239 (P = 0.0271);
MVP		0.24
MPC		0.20
ClinPred		0.72	D
GERP RS		4.1
Varity_R		0.29
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-87912225;