chr17-50863068-T-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005749.4(TOB1):​c.950A>G​(p.Asn317Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

TOB1
NM_005749.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

Publications

1 publications found
Variant links:
Genes affected
TOB1 (HGNC:11979): (transducer of ERBB2, 1) This gene encodes a member of the transducer of erbB-2 /B-cell translocation gene protein family. Members of this family are anti-proliferative factors that have the potential to regulate cell growth. The encoded protein may function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.32666135).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOB1NM_005749.4 linkc.950A>G p.Asn317Ser missense_variant Exon 2 of 2 ENST00000499247.3 NP_005740.1 P50616
TOB1NM_001243877.2 linkc.950A>G p.Asn317Ser missense_variant Exon 3 of 3 NP_001230806.1 P50616
TOB1NM_001243885.2 linkc.533A>G p.Asn178Ser missense_variant Exon 2 of 2 NP_001230814.1 P50616

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TOB1ENST00000499247.3 linkc.950A>G p.Asn317Ser missense_variant Exon 2 of 2 1 NM_005749.4 ENSP00000427695.1 P50616
TOB1ENST00000268957.3 linkc.950A>G p.Asn317Ser missense_variant Exon 3 of 3 1 ENSP00000268957.3 P50616

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152170
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000636
AC:
16
AN:
251452
AF XY:
0.0000589
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461888
Hom.:
0
Cov.:
48
AF XY:
0.0000440
AC XY:
32
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.000151
AC:
6
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.000112
AC:
6
AN:
53418
Middle Eastern (MID)
AF:
0.000347
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000459
AC:
51
AN:
1112008
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000526
AC:
8
AN:
152170
Hom.:
0
Cov.:
31
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41436
American (AMR)
AF:
0.00
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.000188
AC:
2
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68022
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000201
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 12, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.950A>G (p.N317S) alteration is located in exon 2 (coding exon 1) of the TOB1 gene. This alteration results from a A to G substitution at nucleotide position 950, causing the asparagine (N) at amino acid position 317 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
0.066
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
.;D
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.0
L;L
PhyloP100
7.6
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.80
N;N
REVEL
Benign
0.076
Sift
Benign
0.069
T;T
Sift4G
Benign
0.68
T;T
Polyphen
0.011
B;B
Vest4
0.72
MVP
0.17
MPC
0.25
ClinPred
0.078
T
GERP RS
5.8
Varity_R
0.088
gMVP
0.30
Mutation Taster
=67/33
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

Publications

Other links and lift over

dbSNP: rs199928565; hg19: chr17-48940429; API