11-55264911-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229

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

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
TRIM48	NM_024114.5	c.56C>A	p.Ser19Tyr	missense_variant	Exon 2 of 6	ENST00000417545.5	NP_077019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM48	ENST00000417545.5	c.56C>A	p.Ser19Tyr	missense_variant	Exon 2 of 6	1	NM_024114.5	ENSP00000402414.2

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

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;