Variant 11-90038694-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001195234.1(TRIM49C):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: not found (cov: 15)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense, splice_region

Scores

Splicing: ADA: 0.00001450

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.764

Variant links:

Genes affected

TRIM49C (HGNC:38877): (tripartite motif containing 49C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM49C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04391262).

BP6

Variant 11-90038694-C-G is Benign according to our data. Variant chr11-90038694-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2269283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM49C	NM_001195234.1 linkuse as main transcript	c.740C>G	p.Ala247Gly	missense_variant, splice_region_variant	6/8	ENST00000448984.1	NP_001182163.1
TRIM49C	XM_017018126.2 linkuse as main transcript	c.509C>G	p.Ala170Gly	missense_variant, splice_region_variant	3/5		XP_016873615.1
TRIM49C	XM_024448656.2 linkuse as main transcript	c.738+715C>G		intron_variant			XP_024304424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 linkuse as main transcript	c.740C>G	p.Ala247Gly	missense_variant, splice_region_variant	6/8	1	NM_001195234.1	ENSP00000388299	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000107

AC:

AN:

938014

Hom.:

Cov.:

AF XY:

0.00000213

AC XY:

AN XY:

468978

show subpopulations

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:

0.00000137

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 04, 2022

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

0.062

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.027

DANN

Benign

0.17

DEOGEN2

Benign

0.0041

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.027

M_CAP

Benign

0.00035

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.56

REVEL

Benign

0.033

Sift

Benign

0.41

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.067

MutPred

0.53

Loss of stability (P = 0.042);

MVP

0.014

MPC

1.7

ClinPred

0.034

GERP RS

-2.2

Varity_R

0.030

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.072

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