1-228394821-C-G

Variant summary

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

The NM_145214.3(TRIM11):​c.1291G>C​(p.Glu431Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TRIM11
NM_145214.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49
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=0.021447927).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM11NM_145214.3 linkc.1291G>C p.Glu431Gln missense_variant Exon 6 of 6 ENST00000284551.11 NP_660215.1 Q96F44-1
TRIM11XM_017002412.3 linkc.1288G>C p.Glu430Gln missense_variant Exon 6 of 6 XP_016857901.1 Q96F44-3
TRIM11XM_011544285.4 linkc.1060G>C p.Glu354Gln missense_variant Exon 5 of 5 XP_011542587.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM11ENST00000284551.11 linkc.1291G>C p.Glu431Gln missense_variant Exon 6 of 6 1 NM_145214.3 ENSP00000284551.6 Q96F44-1
TRIM11ENST00000493030.6 linkc.916G>C p.Glu306Gln missense_variant Exon 5 of 5 1 ENSP00000473360.1 R4GMV1
ENSG00000270094ENST00000602963.1 linkn.159+373C>G intron_variant Intron 1 of 2 4
TRIM11ENST00000602582.5 linkc.*4G>C downstream_gene_variant 3 ENSP00000473574.1 R4GNB9

Frequencies

GnomAD3 genomes
AF:
0.000257
AC:
39
AN:
152034
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000942
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251386
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000257
AC:
39
AN:
152034
Hom.:
0
Cov.:
33
AF XY:
0.000310
AC XY:
23
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.000942
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.000242
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 01, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1291G>C (p.E431Q) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a G to C substitution at nucleotide position 1291, causing the glutamic acid (E) at amino acid position 431 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
0.094
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
11
DANN
Benign
0.061
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.14
T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.021
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.94
.;N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.54
.;N
REVEL
Benign
0.056
Sift
Benign
1.0
.;T
Sift4G
Benign
0.99
T;T
Polyphen
0.0010
.;B
Vest4
0.059
MVP
0.35
MPC
0.39
ClinPred
0.0080
T
GERP RS
2.6
Varity_R
0.037
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs370800532; hg19: chr1-228582522; API