NM_187841.3:c.312T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_187841.3(TRIM54):ā€‹c.312T>Gā€‹(p.Ile104Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

TRIM54
NM_187841.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0140
Variant links:
Genes affected
TRIM54 (HGNC:16008): (tripartite motif containing 54) The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM54NM_187841.3 linkc.312T>G p.Ile104Met missense_variant Exon 2 of 9 ENST00000380075.7 NP_912730.2 Q9BYV2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM54ENST00000380075.7 linkc.312T>G p.Ile104Met missense_variant Exon 2 of 9 1 NM_187841.3 ENSP00000369415.3 Q9BYV2-1
TRIM54ENST00000296098.4 linkc.312T>G p.Ile104Met missense_variant Exon 2 of 10 1 ENSP00000296098.4 Q9BYV2-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461842
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727208
show subpopulations
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:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152054
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.312T>G (p.I104M) alteration is located in exon 2 (coding exon 2) of the TRIM54 gene. This alteration results from a T to G substitution at nucleotide position 312, causing the isoleucine (I) at amino acid position 104 to be replaced by a methionine (M). 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
Pathogenic
0.98
BayesDel_addAF
Uncertain
0.077
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.64
D;.
Eigen
Benign
0.085
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.72
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.039
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Benign
-0.98
T
MutationAssessor
Pathogenic
3.5
M;M
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.9
D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.98
D;D
Vest4
0.93
MutPred
0.75
Gain of phosphorylation at Y108 (P = 0.0772);Gain of phosphorylation at Y108 (P = 0.0772);
MVP
0.72
MPC
0.37
ClinPred
0.99
D
GERP RS
-3.5
Varity_R
0.64
gMVP
0.61

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: rs1678939672; hg19: chr2-27521578; API