22-46793713-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014346.5(TBC1D22A):​c.332G>T​(p.Arg111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R111Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TBC1D22A
NM_014346.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258

Publications

0 publications found
Variant links:
Genes affected
TBC1D22A (HGNC:1309): (TBC1 domain family member 22A) Enables 14-3-3 protein binding activity and protein homodimerization activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.097062975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D22ANM_014346.5 linkc.332G>T p.Arg111Leu missense_variant Exon 3 of 13 ENST00000337137.9 NP_055161.1 Q8WUA7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D22AENST00000337137.9 linkc.332G>T p.Arg111Leu missense_variant Exon 3 of 13 1 NM_014346.5 ENSP00000336724.4 Q8WUA7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000415
AC:
1
AN:
241232
AF XY:
0.00000757
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458926
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725650
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33440
American (AMR)
AF:
0.00
AC:
0
AN:
44580
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26044
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39672
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86072
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52188
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5356
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111308
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60266
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
4.4
DANN
Benign
0.73
DEOGEN2
Benign
0.011
T;T;T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.33
N
LIST_S2
Uncertain
0.88
D;D;D;D;D
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.097
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L;.;.;.
PhyloP100
0.26
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.99
.;N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.33
.;T;T;T;T
Sift4G
Benign
0.45
T;T;T;T;T
Polyphen
0.081, 0.011, 0.0010
.;B;B;B;.
Vest4
0.35
MutPred
0.29
.;Loss of MoRF binding (P = 0.0092);Loss of MoRF binding (P = 0.0092);.;.;
MVP
0.27
MPC
0.56
ClinPred
0.054
T
GERP RS
-7.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.027
gMVP
0.17
Mutation Taster
=87/13
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: rs772304663; hg19: chr22-47189610; API