NM_001195234.1:c.293A>C

Variant names:

• chr11-90035504-A-C
• NM_001195234.1:c.293A>C

Variant summary

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

The NM_001195234.1(TRIM49C):​c.293A>C​(p.Glu98Ala) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: TRIM49C NM_001195234.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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]

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=0.24289542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195234.1. 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
	TRIM49C	NM_001195234.1	MANE Select	c.293A>C	p.Glu98Ala	missense	Exon 3 of 8	NP_001182163.1	P0CI26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49C	ENST00000448984.1	TSL:1 MANE Select	c.293A>C	p.Glu98Ala	missense	Exon 3 of 8	ENSP00000388299.1	P0CI26

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.027	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.051
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.96	D
Vest4		0.19
MutPred		0.56		Loss of disorder (P = 0.0529)
MVP		0.19
MPC		2.7
ClinPred		0.74	D
GERP RS		-0.80
Varity_R		0.17
gMVP		0.088
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr11-89768672;