Variant 7-101087935-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030961.3(TRIM56):c.623C>G(p.Ala208Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,448,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

TRIM56
NM_030961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4036119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM56	NM_030961.3 linkuse as main transcript	c.623C>G	p.Ala208Gly	missense_variant	3/3	ENST00000306085.11	NP_112223.1	Q9BRZ2-1
TRIM56	XM_011516589.4 linkuse as main transcript	c.623C>G	p.Ala208Gly	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.623C>G	p.Ala208Gly	missense_variant	3/3	1	NM_030961.3	ENSP00000305161.6		Q9BRZ2-1
TRIM56	ENST00000412507.1 linkuse as main transcript	c.623C>G	p.Ala208Gly	missense_variant	3/4	1		ENSP00000404186.1		C9JI91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000440

AC:

AN:

227388

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1448198

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720336

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 02, 2024

The c.623C>G (p.A208G) alteration is located in exon 3 (coding exon 1) of the TRIM56 gene. This alteration results from a C to G substitution at nucleotide position 623, causing the alanine (A) at amino acid position 208 to be replaced by a glycine (G). 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

Uncertain

0.43

BayesDel_addAF

Benign

0.0020

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.69

N;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.26

Sift

Benign

0.046

D;T

Sift4G

Uncertain

0.028

D;D

Polyphen

0.99

D;D

Vest4

0.40

MutPred

0.36

Loss of stability (P = 0.0549);Loss of stability (P = 0.0549);

MVP

0.63

MPC

1.4

ClinPred

0.85

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.23

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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