11-5698412-A-G

Position:

• chr11-5698412-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006074.5(TRIM22):​c.617A>G​(p.Glu206Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.523

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]

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]

ACMG classification

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=0.3082072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.617A>G	p.Glu206Gly	missense_variant	4/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.605A>G	p.Glu202Gly	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.617A>G	p.Glu206Gly	missense_variant	4/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.617A>G (p.E206G) alteration is located in exon 4 (coding exon 3) of the TRIM22 gene. This alteration results from a A to G substitution at nucleotide position 617, causing the glutamic acid (E) at amino acid position 206 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	Benign	0.11
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	3.2	M;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Benign	0.056
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.011	D;D;T
Polyphen		1.0	D;P;.
Vest4		0.20
MutPred		0.34		Loss of ubiquitination at K204 (P = 0.0584);.;Loss of ubiquitination at K204 (P = 0.0584);
MVP		0.84
MPC		0.11
ClinPred		0.94	D
GERP RS		0.11
Varity_R		0.082
gMVP		0.16

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

Other links and lift over

dbSNP: rs1439970764; hg19: chr11-5719642;