1-228401064-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145214.3(TRIM11):​c.635G>A​(p.Arg212Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R212W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TRIM11
NM_145214.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60
Variant links:
Genes affected
TRIM11 (HGNC:16281): (tripartite motif containing 11) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008]

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=0.06901181).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM11NM_145214.3 linkc.635G>A p.Arg212Gln missense_variant Exon 3 of 6 ENST00000284551.11 NP_660215.1 Q96F44-1
TRIM11XM_017002412.3 linkc.632G>A p.Arg211Gln missense_variant Exon 3 of 6 XP_016857901.1 Q96F44-3
TRIM11XM_011544285.4 linkc.504+1002G>A intron_variant Intron 2 of 4 XP_011542587.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM11ENST00000284551.11 linkc.635G>A p.Arg212Gln missense_variant Exon 3 of 6 1 NM_145214.3 ENSP00000284551.6 Q96F44-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000366
AC:
9
AN:
245716
Hom.:
0
AF XY:
0.0000299
AC XY:
4
AN XY:
133818
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000273
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1460568
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
726644
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
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:
0.00
Alfa
AF:
0.0000203
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.635G>A (p.R212Q) alteration is located in exon 3 (coding exon 3) of the TRIM11 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a glutamine (Q). 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
0.079
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T;T;.
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.069
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.4
.;L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.0
.;N;N
REVEL
Benign
0.053
Sift
Benign
0.13
.;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.19, 0.74
.;B;P
Vest4
0.11
MVP
0.082
MPC
0.46
ClinPred
0.10
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.079
gMVP
0.56

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: rs771612251; hg19: chr1-228588765; COSMIC: COSV99034306; COSMIC: COSV99034306; API