11-55264911-C-A

Variant summary

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

The NM_024114.5(TRIM48):​c.56C>A​(p.Ser19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

TRIM48
NM_024114.5 missense

Scores

5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.229
Variant links:
Genes affected
TRIM48 (HGNC:19021): (tripartite motif containing 48) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.19810113).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM48NM_024114.5 linkc.56C>A p.Ser19Tyr missense_variant Exon 2 of 6 ENST00000417545.5 NP_077019.2 Q8IWZ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM48ENST00000417545.5 linkc.56C>A p.Ser19Tyr missense_variant Exon 2 of 6 1 NM_024114.5 ENSP00000402414.2 Q8IWZ4

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
30

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.56C>A (p.S19Y) alteration is located in exon 2 (coding exon 2) of the TRIM48 gene. This alteration results from a C to A substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 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
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
17
DANN
Uncertain
0.98
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.012
N
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.49
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Vest4
0.14
MVP
0.48
MPC
0.0089
ClinPred
0.99
D
GERP RS
0.60
gMVP
0.047

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: chr11-55032387; COSMIC: COSV70161001; COSMIC: COSV70161001; API