NM_001382447.1:c.566G>C

Variant names:

• chr7-22493355-C-G
• NM_001382447.1:c.566G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001382447.1(STEAP1B):​c.566G>C​(p.Arg189Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STEAP1B NM_001382447.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10
• Publications: 0 publications found

Genes affected

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382447.1. 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
	STEAP1B	NM_001382447.1	MANE Select	c.566G>C	p.Arg189Thr	missense	Exon 3 of 5	NP_001369376.1	A0A7I2V339
	STEAP1B	NM_001164460.2		c.566G>C	p.Arg189Thr	missense	Exon 3 of 5	NP_001157932.1	Q6NZ63-2
	STEAP1B	NM_207342.3		c.509G>C	p.Arg170Thr	missense	Exon 3 of 5	NP_997225.1	Q6NZ63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP1B	ENST00000678116.1	MANE Select	c.566G>C	p.Arg189Thr	missense	Exon 3 of 5	ENSP00000503251.1	A0A7I2V339
	STEAP1B	ENST00000404369.8	TSL:1	c.566G>C	p.Arg189Thr	missense	Exon 3 of 5	ENSP00000384370.4	Q6NZ63-2
	STEAP1B	ENST00000406890.6	TSL:1	c.509G>C	p.Arg170Thr	missense	Exon 3 of 5	ENSP00000385239.2	Q6NZ63-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.68		Loss of MoRF binding (P = 0.0195)
MVP		0.75
MPC		0.79
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.67
gMVP		0.87
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr7-22532974;