chr11-5696414-C-A

Position:

chr11-5696414-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_006074.5(TRIM22):c.182C>A(p.Thr61Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,614,234 control chromosomes in the GnomAD database, including 7 homozygotes. 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 7 hom. )

Consequence

TRIM22
NM_006074.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -6.44

Variant links:

Genes affected

TRIM22 (HGNC:16379): (tripartite motif containing 22) 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 cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

TRIM22 links:

TRIM5 (HGNC:16276): (tripartite motif containing 5) 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. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062273443).

BP6

Variant 11-5696414-C-A is Benign according to our data. Variant chr11-5696414-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039217.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000667 (975/1461894) while in subpopulation MID AF= 0.018 (104/5768). AF 95% confidence interval is 0.0152. There are 7 homozygotes in gnomad4_exome. There are 509 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM22	NM_006074.5 linkuse as main transcript	c.182C>A	p.Thr61Asn	missense_variant	2/8	ENST00000379965.8	NP_006065.2
TRIM22	NM_001199573.2 linkuse as main transcript	c.182C>A	p.Thr61Asn	missense_variant	2/8		NP_001186502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM22	ENST00000379965.8 linkuse as main transcript	c.182C>A	p.Thr61Asn	missense_variant	2/8	1	NM_006074.5	ENSP00000369299	P1	Q8IYM9-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000913

AC:

229

AN:

250886

Hom.:

AF XY:

0.000905

AC XY:

123

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00615

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000898

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.000667

AC:

975

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

509

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00520

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000485

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.000748

AC:

114

AN:

152340

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000725

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRIM22-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 17, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.030

DANN

Benign

0.78

DEOGEN2

Benign

0.017

T;T;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.28

T;T;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.97

L;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

N;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.013

B;.;B;.

Vest4

0.21

MVP

0.35

MPC

0.061

ClinPred

0.024

GERP RS

-9.2

Varity_R

0.070

gMVP

0.070

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