Variant 7-101087746-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_030961.3(TRIM56):c.434G>A(p.Arg145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,604,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRIM56
NM_030961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.606

Variant links:

Genes affected

TRIM56 (HGNC:19028): (tripartite motif containing 56) Enables RNA binding activity. Predicted to be involved in several processes, including defense response to other organism; positive regulation of macromolecule metabolic process; and protein K63-linked ubiquitination. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM56 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=0.112901986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM56	NM_030961.3 linkuse as main transcript	c.434G>A	p.Arg145His	missense_variant	3/3	ENST00000306085.11
TRIM56	XM_011516589.4 linkuse as main transcript	c.434G>A	p.Arg145His	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM56	ENST00000306085.11 linkuse as main transcript	c.434G>A	p.Arg145His	missense_variant	3/3	1	NM_030961.3	P1	Q9BRZ2-1
TRIM56	ENST00000412507.1 linkuse as main transcript	c.434G>A	p.Arg145His	missense_variant	3/4	1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000177

AC:

AN:

231980

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

127564

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000191

AC:

277

AN:

1451674

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

147

AN XY:

721700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000904

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000935

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.000334

GnomAD4 genome

AF:

0.000190

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000208

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

Nov 21, 2022

The c.434G>A (p.R145H) alteration is located in exon 3 (coding exon 1) of the TRIM56 gene. This alteration results from a G to A substitution at nucleotide position 434, causing the arginine (R) at amino acid position 145 to be replaced by a histidine (H). 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

0.20

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.079

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.079

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.92

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.085

Sift

Uncertain

0.0050

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

1.0

D;D

Vest4

0.26

MVP

0.72

MPC

0.69

ClinPred

0.066

GERP RS

3.9

Varity_R

0.13

gMVP

0.42

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