Genetic Variant STEAP1B:p.Ala196Thr (chr7-22493335-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001382447.1(STEAP1B):c.586G>A(p.Ala196Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000766 in 1,611,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 0 hom. )

Consequence

STEAP1B
NM_001382447.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.07671401).

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.586G>A	p.Ala196Thr	missense	Exon 3 of 5	NP_001369376.1	A0A7I2V339
STEAP1B	NM_001164460.2		c.586G>A	p.Ala196Thr	missense	Exon 3 of 5	NP_001157932.1	Q6NZ63-2
STEAP1B	NM_207342.3		c.529G>A	p.Ala177Thr	missense	Exon 3 of 5	NP_997225.1	Q6NZ63-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STEAP1B	ENST00000678116.1	MANE Select	c.586G>A	p.Ala196Thr	missense	Exon 3 of 5	ENSP00000503251.1	A0A7I2V339
STEAP1B	ENST00000404369.8	TSL:1	c.586G>A	p.Ala196Thr	missense	Exon 3 of 5	ENSP00000384370.4	Q6NZ63-2
STEAP1B	ENST00000406890.6	TSL:1	c.529G>A	p.Ala177Thr	missense	Exon 3 of 5	ENSP00000385239.2	Q6NZ63-1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000539

AC:

135

AN:

250284

AF XY:

0.000561

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000799

AC:

1167

AN:

1459716

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

545

AN XY:

725690

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33424

American (AMR)

AF:

0.000269

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.000506

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000977

AC:

1085

AN:

1110290

Other (OTH)

AF:

0.000663

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.000447

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68036

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000776

Hom.:

Bravo

AF:

0.000552

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000725

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.000772

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

0.33

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.020

MetaRNN

Benign

0.077

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

0.74

PhyloP100

4.4

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.85

REVEL

Benign

0.17

Sift

Benign

0.31

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.56

MVP

0.71

MPC

0.64

ClinPred

0.066

GERP RS

1.2

Varity_R

0.035

gMVP

0.70

Mutation Taster

=83/17

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