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GeneBe

4-188146877-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_178556.5(TRIML1):c.912T>A(p.Asp304Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000003 in 1,333,414 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

TRIML1
NM_178556.5 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.419
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.754

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIML1NM_178556.5 linkuse as main transcriptc.912T>A p.Asp304Glu missense_variant 6/6 ENST00000332517.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIML1ENST00000332517.4 linkuse as main transcriptc.912T>A p.Asp304Glu missense_variant 6/61 NM_178556.5 P1
TRIML1ENST00000507581.5 linkuse as main transcriptn.372T>A non_coding_transcript_exon_variant 3/31
TRIML1ENST00000512233.1 linkuse as main transcriptn.262T>A non_coding_transcript_exon_variant 4/43

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000300
AC:
4
AN:
1333414
Hom.:
0
Cov.:
31
AF XY:
0.00000154
AC XY:
1
AN XY:
650514
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:
0.00000381
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 26, 2023The c.912T>A (p.D304E) alteration is located in exon 6 (coding exon 6) of the TRIML1 gene. This alteration results from a T to A substitution at nucleotide position 912, causing the aspartic acid (D) at amino acid position 304 to be replaced by a glutamic acid (E). 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
0.75
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
Cadd
Benign
22
Dann
Uncertain
1.0
DEOGEN2
Benign
0.14
T
Eigen
Benign
0.15
Eigen_PC
Benign
0.026
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.030
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
0.61
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.20
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.68
Gain of glycosylation at S307 (P = 0.0474);
MVP
0.44
MPC
0.26
ClinPred
0.97
D
GERP RS
3.7
Varity_R
0.34
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-189068031; API