Genetic Variant STEAP1B:p.Thr32Met (chr7-22493826-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001382447.1(STEAP1B):c.95C>T(p.Thr32Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,600,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

STEAP1B
NM_001382447.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

Publications

0 publications found

Variant links:

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]

STEAP1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06665924).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP1B	NM_001382447.1	MANE Select	c.95C>T	p.Thr32Met	missense	Exon 3 of 5	NP_001369376.1	A0A7I2V339
STEAP1B	NM_001164460.2		c.95C>T	p.Thr32Met	missense	Exon 3 of 5	NP_001157932.1	Q6NZ63-2
STEAP1B	NM_207342.3		c.85-47C>T		intron	N/A	NP_997225.1	Q6NZ63-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP1B	ENST00000678116.1	MANE Select	c.95C>T	p.Thr32Met	missense	Exon 3 of 5	ENSP00000503251.1	A0A7I2V339
STEAP1B	ENST00000404369.8	TSL:1	c.95C>T	p.Thr32Met	missense	Exon 3 of 5	ENSP00000384370.4	Q6NZ63-2
STEAP1B	ENST00000406890.6	TSL:1	c.85-47C>T		intron	N/A	ENSP00000385239.2	Q6NZ63-1

Frequencies

GnomAD3 genomes

AF:

0.0000335

AC:

AN:

149444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247508

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1451158

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

721544

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33122

American (AMR)

AF:

0.00

AC:

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000997

AC:

AN:

1103068

Other (OTH)

AF:

0.0000333

AC:

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000335

AC:

AN:

149444

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72768

show subpopulations

African (AFR)

AF:

0.0000495

AC:

AN:

40404

American (AMR)

AF:

0.00

AC:

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67246

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000825

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.67

M_CAP

Benign

0.0026

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.99

PhyloP100

2.9

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.97

REVEL

Benign

0.11

Sift

Benign

0.27

Sift4G

Benign

0.14

Vest4

0.16

MutPred

0.10

Loss of phosphorylation at T32 (P = 0.142)

MVP

0.030

MPC

0.16

ClinPred

0.046

GERP RS

1.1

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over