11-90035504-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

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=0.24289542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM49C	NM_001195234.1	c.293A>C	p.Glu98Ala	missense_variant	Exon 3 of 8	ENST00000448984.1	NP_001182163.1
TRIM49C	XM_024448656.2	c.293A>C	p.Glu98Ala	missense_variant	Exon 1 of 6		XP_024304424.1
TRIM49C	XM_017018126.2	c.293A>C	p.Glu98Ala	missense_variant	Exon 1 of 5		XP_016873615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1	c.293A>C	p.Glu98Ala	missense_variant	Exon 3 of 8	1	NM_001195234.1	ENSP00000388299.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293A>C (p.E98A) alteration is located in exon 3 (coding exon 1) of the TRIM49C gene. This alteration results from a A to C substitution at nucleotide position 293, causing the glutamic acid (E) at amino acid position 98 to be replaced by an alanine (A). 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
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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-89768672;