22-41436985-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016272.4(TOB2):​c.361G>A​(p.Gly121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TOB2
NM_016272.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
Variant links:
Genes affected
TOB2 (HGNC:11980): (transducer of ERBB2, 2) TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.014762253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOB2NM_016272.4 linkc.361G>A p.Gly121Ser missense_variant Exon 2 of 2 ENST00000327492.4 NP_057356.1 Q14106-1
TOB2XM_005261315.3 linkc.361G>A p.Gly121Ser missense_variant Exon 2 of 2 XP_005261372.1 Q14106-1
TOB2XM_006724105.4 linkc.361G>A p.Gly121Ser missense_variant Exon 2 of 2 XP_006724168.1 Q14106-1
TOB2XM_017028539.2 linkc.361G>A p.Gly121Ser missense_variant Exon 2 of 2 XP_016884028.1 Q14106-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOB2ENST00000327492.4 linkc.361G>A p.Gly121Ser missense_variant Exon 2 of 2 1 NM_016272.4 ENSP00000331305.3 Q14106-1
TOB2ENST00000434408.1 linkc.*57G>A downstream_gene_variant 2 ENSP00000388549.2 B0QXZ4

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000821
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251358
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1461890
Hom.:
0
Cov.:
30
AF XY:
0.0000275
AC XY:
20
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000794
Hom.:
0
Bravo
AF:
0.000283
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.361G>A (p.G121S) alteration is located in exon 2 (coding exon 1) of the TOB2 gene. This alteration results from a G to A substitution at nucleotide position 361, causing the glycine (G) at amino acid position 121 to be replaced by a serine (S). 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
0.061
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.015
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.087
Sift
Benign
0.068
T
Sift4G
Benign
0.15
T
Polyphen
0.37
B
Vest4
0.060
MVP
0.23
MPC
0.32
ClinPred
0.041
T
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.064
gMVP
0.37

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.

Other links and lift over

dbSNP: rs150938078; hg19: chr22-41832989; API