Genetic Variant TRIM11:p.Gly462Arg (chr1-228394728-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_145214.3(TRIM11):c.1384G>A(p.Gly462Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

TRIM11
NM_145214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

TRIM11 (HGNC:16281): (tripartite motif containing 11) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008]

TRIM11 links:

ENSG00000270094 (HGNC:):

ENSG00000270094 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=0.31162935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3 link	c.1384G>A	p.Gly462Arg	missense_variant	Exon 6 of 6	ENST00000284551.11	NP_660215.1	Q96F44-1
TRIM11	XM_017002412.3 link	c.1381G>A	p.Gly461Arg	missense_variant	Exon 6 of 6		XP_016857901.1	Q96F44-3
TRIM11	XM_011544285.4 link	c.1153G>A	p.Gly385Arg	missense_variant	Exon 5 of 5		XP_011542587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM11	ENST00000284551.11 link	c.1384G>A	p.Gly462Arg	missense_variant	Exon 6 of 6	1	NM_145214.3	ENSP00000284551.6	Q96F44-1
TRIM11	ENST00000493030.6 link	c.1009G>A	p.Gly337Arg	missense_variant	Exon 5 of 5	1		ENSP00000473360.1	R4GMV1
ENSG00000270094	ENST00000602963.1 link	n.159+280C>T		intron_variant	Intron 1 of 2	4
TRIM11	ENST00000602582.5 link	c.*97G>A		downstream_gene_variant		3		ENSP00000473574.1	R4GNB9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247062

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133672

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:

0.0000999

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455652

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1384G>A (p.G462R) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a G to A substitution at nucleotide position 1384, causing the glycine (G) at amino acid position 462 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.067

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.9

.;D

REVEL

Uncertain

0.29

Sift

Benign

0.045

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.34

MutPred

0.21

.;Loss of glycosylation at S461 (P = 0.0426);

MVP

0.61

MPC

1.3

ClinPred

0.92

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.60

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