11-49032310-A-G

Position:

• chr11-49032310-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000332682.9(TRIM49B):​c.446A>G​(p.Glu149Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM49B ENST00000332682.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.583

Genes affected

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

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=0.1584712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2	c.446A>G	p.Glu149Gly	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.446A>G	p.Glu149Gly	missense_variant	3/7	1	NM_001206626.2	ENSP00000330216.7
TRIM49B	ENST00000622138.4	c.446A>G	p.Glu149Gly	missense_variant	4/8	1		ENSP00000481457.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000411 AC: 6 AN: 1461166 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 726914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

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

Mar 18, 2024

The c.446A>G (p.E149G) alteration is located in exon 2 (coding exon 2) of the TRIM49B gene. This alteration results from a A to G substitution at nucleotide position 446, causing the glutamic acid (E) at amino acid position 149 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	Benign	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.099	T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.28	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.4	.;D
REVEL	Benign	0.14
Sift	Benign	0.11	.;T
Sift4G	Benign	0.078	T;T
Vest4		0.17
MutPred		0.47		Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);
MVP		0.39
MPC		2.0
ClinPred		0.41	T
GERP RS		0.49
Varity_R		0.13
gMVP		0.044

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: chr11-49053862;