Variant 11-49032326-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001206626.2(TRIM49B):c.462T>A(p.Asn154Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,114 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

TRIM49B
NM_001206626.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.406

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020580888).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2 linkuse as main transcript	c.462T>A	p.Asn154Lys	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 linkuse as main transcript	c.462T>A	p.Asn154Lys	missense_variant	3/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4 linkuse as main transcript	c.462T>A	p.Asn154Lys	missense_variant	4/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes

AF:

0.000797

AC:

121

AN:

151740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000965

GnomAD3 exomes

AF:

0.000708

AC:

174

AN:

245650

Hom.:

AF XY:

0.000733

AC XY:

AN XY:

133754

show subpopulations

Gnomad AFR exome

AF:

0.000268

Gnomad AMR exome

AF:

0.000469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00143

AC:

2095

AN:

1461256

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1009

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000797

AC:

121

AN:

151858

Hom.:

Cov.:

AF XY:

0.000728

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000726

Hom.:

Bravo

AF:

0.000774

ExAC

AF:

0.000694

AC:

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

Jul 13, 2021

The c.462T>A (p.N154K) alteration is located in exon 2 (coding exon 2) of the TRIM49B gene. This alteration results from a T to A substitution at nucleotide position 462, causing the asparagine (N) at amino acid position 154 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.3

.;D

REVEL

Benign

0.075

Sift

Benign

0.13

.;T

Sift4G

Benign

0.72

T;T

Vest4

0.31

MutPred

0.47

Gain of ubiquitination at N154 (P = 0.0138);Gain of ubiquitination at N154 (P = 0.0138);

MVP

0.061

MPC

2.1

ClinPred

0.033

GERP RS

-0.80

Varity_R

0.27

gMVP

0.049

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