Genetic Variant STEAP1B:p.Ala196Thr (chr7-22493335-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/21 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1B	NM_001382447.1 link	c.586G>A	p.Ala196Thr	missense_variant	Exon 3 of 5	ENST00000678116.1	NP_001369376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP1B	ENST00000678116.1 link	c.586G>A	p.Ala196Thr	missense_variant	Exon 3 of 5		NM_001382447.1	ENSP00000503251.1		A0A7I2V339

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

GnomAD3 exomes

AF:

0.000539

AC:

135

AN:

250284

Hom.:

AF XY:

0.000561

AC XY:

AN XY:

135358

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.000977

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.000447

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000734

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586G>A (p.A196T) alteration is located in exon 3 (coding exon 2) of the STEAP1B gene. This alteration results from a G to A substitution at nucleotide position 586, causing the alanine (A) at amino acid position 196 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;T;T

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

0.74

N;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.85

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.31

T;T;T;T

Sift4G

Benign

0.28

T;T;T;.

Polyphen

1.0

D;.;.;.

Vest4

0.56

MVP

0.71

MPC

0.64

ClinPred

0.066

GERP RS

1.2

Varity_R

0.035

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over