Variant 5-181260602-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001346048.2(TRIM52):c.212C>T(p.Ala71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TRIM52
NM_001346048.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

Variant links:

Genes affected

TRIM52 (HGNC:19024): (tripartite motif containing 52) Enables transcription coactivator activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of NF-kappaB transcription factor activity; and protein autoubiquitination. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRIM52 links:

CTC-338M12.4 (HGNC:):

CTC-338M12.4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026133955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM52	NM_001346048.2 linkuse as main transcript	c.212C>T	p.Ala71Val	missense_variant	1/2	ENST00000688015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM52	ENST00000688015.1 linkuse as main transcript	c.212C>T	p.Ala71Val	missense_variant	1/2		NM_001346048.2	A2
CTC-338M12.4	ENST00000511331.5 linkuse as main transcript	n.632-10971G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250452

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151624

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

Nov 07, 2022

The c.212C>T (p.A71V) alteration is located in exon 1 (coding exon 1) of the TRIM52 gene. This alteration results from a C to T substitution at nucleotide position 212, causing the alanine (A) at amino acid position 71 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0092

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.55

M_CAP

Benign

0.0020

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.23

Polyphen

0.011

Vest4

0.066

MVP

0.014

ClinPred

0.028

GERP RS

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.20

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