rs759208465

Variant names:

• chr11-55265285-C-A
• rs759208465
• NM_024114.5:c.430C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-55265285-C-A
• chr11-55265285-C-T

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.430C>A​(p.Pro144Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 147,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. P144S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 30)
• Consequence: TRIM48 NM_024114.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• 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=0.23412654).

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.430C>A	p.Pro144Thr	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.430C>A	p.Pro144Thr	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes AF: 0.00000678 AC: 1 AN: 147506 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000678 AC: 1 AN: 147506 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 1 AN XY: 71776

African (AFR) AF: 0.0000248 AC: 1 AN: 40316

American (AMR) AF: 0.00 AC: 0 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 4586

South Asian (SAS) AF: 0.00 AC: 0 AN: 4082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66844

Other (OTH) AF: 0.00 AC: 0 AN: 2016

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000552

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.072	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.88	T
PhyloP100		1.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.10
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Vest4		0.34
MVP		0.26
MPC		0.0058
ClinPred		0.97	D
GERP RS		0.60
gMVP		0.033
Mutation Taster		=98/2	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: rs759208465; hg19: chr11-55032761;