11-55264911-C-G

Variant names:

• chr11-55264911-C-G
• rs1857362119
• NM_024114.5:c.56C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024114.5(TRIM48):​c.56C>G​(p.Ser19Cys) 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. 14/20 in silico tools predict a benign outcome for this variant. 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. S19Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TRIM48 NM_024114.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17653564).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM48	NM_024114.5	MANE Select	c.56C>G	p.Ser19Cys	missense	Exon 2 of 6	NP_077019.2	Q8IWZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM48	ENST00000417545.5	TSL:1 MANE Select	c.56C>G	p.Ser19Cys	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.57	T
PhyloP100		0.23
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Vest4		0.14
MVP		0.36
MPC		0.011
ClinPred		0.72	D
GERP RS		0.60
gMVP		0.044
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1857362119; hg19: chr11-55032387;