11-90035435-C-T

Variant summary

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

The NM_001195234.1(TRIM49C):​c.224C>T​(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 1,364,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)
Exomes 𝑓: 0.0000066 ( 1 hom. )

Consequence

TRIM49C
NM_001195234.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.945
Variant links:
Genes affected
TRIM49C (HGNC:38877): (tripartite motif containing 49C) 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]

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=0.079000086).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM49CNM_001195234.1 linkc.224C>T p.Ser75Phe missense_variant Exon 3 of 8 ENST00000448984.1 NP_001182163.1 P0CI26
TRIM49CXM_024448656.2 linkc.224C>T p.Ser75Phe missense_variant Exon 1 of 6 XP_024304424.1
TRIM49CXM_017018126.2 linkc.224C>T p.Ser75Phe missense_variant Exon 1 of 5 XP_016873615.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM49CENST00000448984.1 linkc.224C>T p.Ser75Phe missense_variant Exon 3 of 8 1 NM_001195234.1 ENSP00000388299.1 P0CI26

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD4 exome
AF:
0.00000660
AC:
9
AN:
1364530
Hom.:
1
Cov.:
33
AF XY:
0.00000442
AC XY:
3
AN XY:
679308
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:
0.00
Gnomad4 OTH exome
AF:
0.000158
GnomAD4 genome
Cov.:
19

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.224C>T (p.S75F) alteration is located in exon 3 (coding exon 1) of the TRIM49C gene. This alteration results from a C to T substitution at nucleotide position 224, causing the serine (S) at amino acid position 75 to be replaced by a phenylalanine (F). 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
0.16
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
1.3
DANN
Benign
0.48
DEOGEN2
Benign
0.092
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0016
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.16
Sift
Benign
0.13
T
Sift4G
Benign
0.12
T
Polyphen
0.044
B
Vest4
0.10
MutPred
0.43
Loss of phosphorylation at S75 (P = 0.0499);
MVP
0.12
MPC
1.9
ClinPred
0.056
T
GERP RS
-1.5
Varity_R
0.072
gMVP
0.046

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: rs748897739; hg19: chr11-89768603; API