1-228395250-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145214.3(TRIM11):​c.862G>T​(p.Asp288Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TRIM11
NM_145214.3 missense, splice_region

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM11NM_145214.3 linkc.862G>T p.Asp288Tyr missense_variant, splice_region_variant Exon 6 of 6 ENST00000284551.11 NP_660215.1 Q96F44-1
TRIM11XM_017002412.3 linkc.859G>T p.Asp287Tyr missense_variant, splice_region_variant Exon 6 of 6 XP_016857901.1 Q96F44-3
TRIM11XM_011544285.4 linkc.631G>T p.Asp211Tyr missense_variant, splice_region_variant Exon 5 of 5 XP_011542587.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM11ENST00000284551.11 linkc.862G>T p.Asp288Tyr missense_variant, splice_region_variant Exon 6 of 6 1 NM_145214.3 ENSP00000284551.6 Q96F44-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1306120
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
634628
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 31, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.862G>T (p.D288Y) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a G to T substitution at nucleotide position 862, causing the aspartic acid (D) at amino acid position 288 to be replaced by a tyrosine (Y). 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
0.25
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-6.8
.;D
REVEL
Benign
0.19
Sift
Pathogenic
0.0
.;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.76
.;P
Vest4
0.66
MutPred
0.50
.;Loss of disorder (P = 0.004);
MVP
0.41
MPC
1.3
ClinPred
0.98
D
GERP RS
5.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.76
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-228582951; COSMIC: COSV52857534; COSMIC: COSV52857534; API