Genetic Variant TRIM11:p.Glu431Gln (chr1-228394821-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_145214.3(TRIM11):c.1291G>C(p.Glu431Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TRIM11
NM_145214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

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 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=0.021447927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM11	NM_145214.3 link	c.1291G>C	p.Glu431Gln	missense_variant	Exon 6 of 6	ENST00000284551.11	NP_660215.1	Q96F44-1
TRIM11	XM_017002412.3 link	c.1288G>C	p.Glu430Gln	missense_variant	Exon 6 of 6		XP_016857901.1	Q96F44-3
TRIM11	XM_011544285.4 link	c.1060G>C	p.Glu354Gln	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.1291G>C	p.Glu431Gln	missense_variant	Exon 6 of 6	1	NM_145214.3	ENSP00000284551.6	Q96F44-1
TRIM11	ENST00000493030.6 link	c.916G>C	p.Glu306Gln	missense_variant	Exon 5 of 5	1		ENSP00000473360.1	R4GMV1
ENSG00000270094	ENST00000602963.1 link	n.159+373C>G		intron_variant	Intron 1 of 2	4
TRIM11	ENST00000602582.5 link	c.*4G>C		downstream_gene_variant		3		ENSP00000473574.1	R4GNB9

Frequencies

GnomAD3 genomes

AF:

0.000257

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251386

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000289

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:

0.0000198

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000331

GnomAD4 genome

AF:

0.000257

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.000942

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000242

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1291G>C (p.E431Q) alteration is located in exon 6 (coding exon 6) of the TRIM11 gene. This alteration results from a G to C substitution at nucleotide position 1291, causing the glutamic acid (E) at amino acid position 431 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.061

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.14

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.94

.;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.54

.;N

REVEL

Benign

0.056

Sift

Benign

1.0

.;T

Sift4G

Benign

0.99

T;T

Polyphen

0.0010

.;B

Vest4

0.059

MVP

0.35

MPC

0.39

ClinPred

0.0080

GERP RS

2.6

Varity_R

0.037

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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