chr1-228401056-C-T

Variant summary

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

The NM_145214.3(TRIM11):​c.643G>A​(p.Ala215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,490 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 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TRIM11
NM_145214.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17
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 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=0.029768616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM11NM_145214.3 linkc.643G>A p.Ala215Thr missense_variant Exon 3 of 6 ENST00000284551.11 NP_660215.1 Q96F44-1
TRIM11XM_017002412.3 linkc.640G>A p.Ala214Thr missense_variant Exon 3 of 6 XP_016857901.1 Q96F44-3
TRIM11XM_011544285.4 linkc.504+1010G>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.643G>A p.Ala215Thr missense_variant Exon 3 of 6 1 NM_145214.3 ENSP00000284551.6 Q96F44-1

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000451
AC:
11
AN:
243968
Hom.:
0
AF XY:
0.0000376
AC XY:
5
AN XY:
133032
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000263
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000920
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1460150
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
726410
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000247
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152340
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.000253
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.643G>A (p.A215T) 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 643, causing the alanine (A) at amino acid position 215 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
0.089
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
18
DANN
Benign
0.80
DEOGEN2
Benign
0.016
T;T;.
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.1
.;L;L
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.5
.;N;N
REVEL
Benign
0.010
Sift
Benign
0.39
.;T;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.067, 0.54
.;B;P
Vest4
0.18
MutPred
0.36
.;Gain of phosphorylation at A215 (P = 0.0441);Gain of phosphorylation at A215 (P = 0.0441);
MVP
0.043
MPC
0.38
ClinPred
0.026
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.053
gMVP
0.39

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: rs558730848; hg19: chr1-228588757; COSMIC: COSV52859707; COSMIC: COSV52859707; API