11-49032366-T-G

Position:

• chr11-49032366-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001206626.2(TRIM49B):​c.502T>G​(p.Trp168Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRIM49B NM_001206626.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

Genes affected

TRIM49B (HGNC:42955): (tripartite motif containing 49B)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.375844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2	c.502T>G	p.Trp168Gly	missense_variant	3/7	ENST00000332682.9	NP_001193555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49B	ENST00000332682.9	c.502T>G	p.Trp168Gly	missense_variant	3/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4	c.502T>G	p.Trp168Gly	missense_variant	4/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.502T>G (p.W168G) alteration is located in exon 2 (coding exon 2) of the TRIM49B gene. This alteration results from a T to G substitution at nucleotide position 502, causing the tryptophan (W) at amino acid position 168 to be replaced by a glycine (G). 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	Pathogenic	0.73
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.55
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-10	.;D
REVEL	Benign	0.073
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0050	D;D
Vest4		0.46
MutPred		0.55		Loss of catalytic residue at W168 (P = 0.0057);Loss of catalytic residue at W168 (P = 0.0057);
MVP		0.13
MPC		3.9
ClinPred		0.75	D
GERP RS		0.11
Varity_R		0.41
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs771251284; hg19: chr11-49053918;