Variant chr7-101087680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000306085.11(TRIM56):c.368G>A(p.Cys123Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TRIM56
ENST00000306085.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM56	NM_030961.3 linkuse as main transcript	c.368G>A	p.Cys123Tyr	missense_variant	3/3	ENST00000306085.11	NP_112223.1	Q9BRZ2-1
TRIM56	XM_011516589.4 linkuse as main transcript	c.368G>A	p.Cys123Tyr	missense_variant	2/2		XP_011514891.1	Q9BRZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM56	ENST00000306085.11 linkuse as main transcript	c.368G>A	p.Cys123Tyr	missense_variant	3/3	1	NM_030961.3	ENSP00000305161.6		Q9BRZ2-1
TRIM56	ENST00000412507.1 linkuse as main transcript	c.368G>A	p.Cys123Tyr	missense_variant	3/4	1		ENSP00000404186.1		C9JI91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000448

AC:

AN:

223012

Hom.:

AF XY:

0.00

AC XY:

AN XY:

122434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000310

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443654

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000837

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

Jun 29, 2022

The c.368G>A (p.C123Y) 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 368, causing the cysteine (C) at amino acid position 123 to be replaced by a tyrosine (Y). 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

1.0

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-11

D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.064

T;D

Polyphen

1.0

D;D

Vest4

0.80

MutPred

0.61

Loss of disorder (P = 0.0382);Loss of disorder (P = 0.0382);

MVP

0.92

MPC

1.9

ClinPred

1.0

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.94

gMVP

0.90

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