4-188146822-C-G

Variant summary

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

The NM_178556.5(TRIML1):​c.857C>G​(p.Thr286Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000737 in 1,357,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T286K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000066 ( 0 hom. )

Consequence

TRIML1
NM_178556.5 missense, splice_region

Scores

19
Splicing: ADA: 0.0007144
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11
Variant links:
Genes affected
TRIML1 (HGNC:26698): (tripartite motif family like 1) The protein encoded by this gene is a tripartite motif family protein with similarities to E3 ubiquitin-protein ligases. While the function of the encoded protein has not been determined, the orthologous protein in mouse has been shown to bind ubiquitin-specific protease 5 and is involved in the blastocyst development stage. [provided by RefSeq, Sep 2016]

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=0.09847057).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIML1NM_178556.5 linkc.857C>G p.Thr286Arg missense_variant, splice_region_variant Exon 6 of 6 ENST00000332517.4 NP_848651.2 Q8N9V2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIML1ENST00000332517.4 linkc.857C>G p.Thr286Arg missense_variant, splice_region_variant Exon 6 of 6 1 NM_178556.5 ENSP00000327738.3 Q8N9V2
TRIML1ENST00000507581.5 linkn.317C>G splice_region_variant, non_coding_transcript_exon_variant Exon 3 of 3 1
TRIML1ENST00000512233.1 linkn.207C>G splice_region_variant, non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000151
AC:
2
AN:
132062
Hom.:
0
AF XY:
0.0000142
AC XY:
1
AN XY:
70424
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000122
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000664
AC:
8
AN:
1205434
Hom.:
0
Cov.:
30
AF XY:
0.00000345
AC XY:
2
AN XY:
579396
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:
0.000186
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000268
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
14
DANN
Benign
0.47
DEOGEN2
Benign
0.0049
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.22
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
-0.88
N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
0.31
N
REVEL
Benign
0.17
Sift
Benign
0.20
T
Sift4G
Benign
0.53
T
Polyphen
0.66
P
Vest4
0.38
MutPred
0.57
Gain of MoRF binding (P = 0.0152);
MVP
0.29
MPC
0.086
ClinPred
0.15
T
GERP RS
4.0
Varity_R
0.12
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00071
dbscSNV1_RF
Benign
0.14
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: rs779588753; hg19: chr4-189067976; API