rs376578471

Variant names:

• chr7-90225497-G-T
• rs376578471
• NM_001244944.2:c.415G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-90225497-G-T
• chr7-90225497-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001244944.2(STEAP2):​c.415G>T​(p.Asp139Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,613,750 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (7 hom.)
• Consequence: STEAP2 NM_001244944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66
• Publications: 1 publications found

Genes affected

STEAP2 (HGNC:17885): (STEAP2 metalloreductase) This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3115456).
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244944.2. 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
	STEAP2	NM_001244944.2	MANE Select	c.415G>T	p.Asp139Tyr	missense	Exon 3 of 6	NP_001231873.1	Q8NFT2-1
	STEAP2	NM_001040665.2		c.415G>T	p.Asp139Tyr	missense	Exon 3 of 6	NP_001035755.1	Q8NFT2-1
	STEAP2	NM_152999.4		c.415G>T	p.Asp139Tyr	missense	Exon 2 of 5	NP_694544.2	Q8NFT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP2	ENST00000394621.7	TSL:1 MANE Select	c.415G>T	p.Asp139Tyr	missense	Exon 3 of 6	ENSP00000378119.2	Q8NFT2-1
	STEAP2	ENST00000287908.7	TSL:1	c.415G>T	p.Asp139Tyr	missense	Exon 2 of 5	ENSP00000287908.3	Q8NFT2-1
	STEAP2	ENST00000394622.6	TSL:1	c.415G>T	p.Asp139Tyr	missense	Exon 3 of 6	ENSP00000378120.2	Q8NFT2-1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000877 AC: 22 AN: 250984 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000102 AC: 149 AN: 1461516 Hom.: 7 Cov.: 33 AF XY: 0.000107 AC XY: 78 AN XY: 727030

African (AFR) AF: 0.000329 AC: 11 AN: 33458

American (AMR) AF: 0.000134 AC: 6 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5762

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111840

Other (OTH) AF: 0.000132 AC: 8 AN: 60378

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00111 AC: 17 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000773 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.25
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.042	D
Polyphen		0.94	P
Vest4		0.63
MVP		0.44
MPC		0.14
ClinPred		0.20	T
GERP RS		5.7
Varity_R		0.47
gMVP		0.77
Mutation Taster		=59/41	polymorphism

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: rs376578471; hg19: chr7-89854811; COSMIC: COSV55294156; COSMIC: COSV55294156;