11-55265002-C-A

Variant names:

• chr11-55265002-C-A
• rs143766722
• NM_024114.5:c.147C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024114.5(TRIM48):​c.147C>A​(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIM48 NM_024114.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27350777).

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.147C>A	p.Ser49Arg	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.147C>A	p.Ser49Arg	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436590 Hom.: 0 Cov.: 32 AF XY: 0.00000280 AC XY: 2 AN XY: 713690

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 43884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.00 AC: 0 AN: 36822

South Asian (SAS) AF: 0.00 AC: 0 AN: 79630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5348

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1099450

Other (OTH) AF: 0.00 AC: 0 AN: 59270

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.94
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.23	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.029	D
Vest4		0.27
MVP		0.25
MPC		0.0073
ClinPred		0.58	D
GERP RS		-1.2
gMVP		0.065
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: rs143766722; hg19: chr11-55032478;