7-22493607-T-C

Variant names:

• chr7-22493607-T-C
• NM_001382447.1:c.314A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382447.1(STEAP1B):​c.314A>G​(p.Tyr105Cys) 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. 13/22 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: STEAP1B NM_001382447.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.817
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16758487).

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.314A>G	p.Tyr105Cys	missense	Exon 3 of 5	NP_001369376.1	A0A7I2V339
	STEAP1B	NM_001164460.2		c.314A>G	p.Tyr105Cys	missense	Exon 3 of 5	NP_001157932.1	Q6NZ63-2
	STEAP1B	NM_207342.3		c.257A>G	p.Tyr86Cys	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.314A>G	p.Tyr105Cys	missense	Exon 3 of 5	ENSP00000503251.1	A0A7I2V339
	STEAP1B	ENST00000404369.8	TSL:1	c.314A>G	p.Tyr105Cys	missense	Exon 3 of 5	ENSP00000384370.4	Q6NZ63-2
	STEAP1B	ENST00000406890.6	TSL:1	c.257A>G	p.Tyr86Cys	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	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.82
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.095
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.16
MutPred		0.20		Gain of catalytic residue at K89 (P = 0.121)
MVP		0.13
MPC		0.21
ClinPred		0.29	T
GERP RS		1.1
Varity_R		0.083
gMVP		0.58
Mutation Taster		=92/8	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

hg19: chr7-22533226;