Variant 11-49034233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206626.2(TRIM49B):c.595G>A(p.Glu199Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00009 in 1,611,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

TRIM49B
NM_001206626.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.150

Variant links:

Genes affected

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

TRIM49B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14952075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2 linkuse as main transcript	c.595G>A	p.Glu199Lys	missense_variant	4/7	ENST00000332682.9	NP_001193555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49B	ENST00000332682.9 linkuse as main transcript	c.595G>A	p.Glu199Lys	missense_variant	4/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4 linkuse as main transcript	c.595G>A	p.Glu199Lys	missense_variant	5/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000841

AC:

AN:

249768

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000945

AC:

138

AN:

1459650

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.595G>A (p.E199K) alteration is located in exon 3 (coding exon 3) of the TRIM49B gene. This alteration results from a G to A substitution at nucleotide position 595, causing the glutamic acid (E) at amino acid position 199 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.1

.;D

REVEL

Benign

0.033

Sift

Uncertain

0.024

.;D

Sift4G

Uncertain

0.0080

D;D

Vest4

0.23

MutPred

0.55

Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);

MVP

0.10

MPC

2.2

ClinPred

0.14

GERP RS

-1.0

Varity_R

0.24

gMVP

0.073

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over