Variant 11-49035096-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001206626.2(TRIM49B):c.740C>G(p.Ala247Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000025 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49B
NM_001206626.2 missense, splice_region

Scores

Splicing: ADA: 0.00008279

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.85

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07669017).

BP6

Variant 11-49035096-C-G is Benign according to our data. Variant chr11-49035096-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2375971.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2 linkuse as main transcript	c.740C>G	p.Ala247Gly	missense_variant, splice_region_variant	5/7	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.740C>G	p.Ala247Gly	missense_variant, splice_region_variant	5/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4 linkuse as main transcript	c.740C>G	p.Ala247Gly	missense_variant, splice_region_variant	6/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

121262

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000305

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:

0.000399

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000149

AC:

AN:

1343876

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

670254

show subpopulations

Gnomad4 AFR exome

AF:

0.0000334

Gnomad4 AMR exome

AF:

0.0000274

Gnomad4 ASJ exome

AF:

0.0000431

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000407

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000183

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000247

AC:

AN:

121262

Hom.:

Cov.:

AF XY:

0.0000351

AC XY:

AN XY:

57034

show subpopulations

Gnomad4 AFR

AF:

0.0000305

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000399

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0050

DANN

Benign

0.22

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00070

LIST_S2

Benign

0.027

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.28

.;N

REVEL

Benign

0.0080

Sift

Benign

0.40

.;T

Sift4G

Benign

0.45

T;T

Vest4

0.072

MutPred

0.42

Loss of stability (P = 0.042);Loss of stability (P = 0.042);

MVP

0.055

MPC

1.8

ClinPred

0.031

GERP RS

0.11

Varity_R

0.036

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.026

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over