chr11-5698387-G-A

Position:

• chr11-5698387-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006074.5(TRIM22):​c.592G>A​(p.Glu198Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.879

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.592G>A	p.Glu198Lys	missense_variant	4/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.580G>A	p.Glu194Lys	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.592G>A	p.Glu198Lys	missense_variant	4/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Dec 19, 2022

The c.592G>A (p.E198K) alteration is located in exon 4 (coding exon 3) of the TRIM22 gene. This alteration results from a G to A substitution at nucleotide position 592, causing the glutamic acid (E) at amino acid position 198 to be replaced by a lysine (K). 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	0.20
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	L;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.051	T;D;T;D
Sift4G	Uncertain	0.0040	D;D;T;D
Polyphen		0.73	P;.;B;.
Vest4		0.32
MutPred		0.63		Gain of ubiquitination at E198 (P = 0.0155);Gain of ubiquitination at E198 (P = 0.0155);.;Gain of ubiquitination at E198 (P = 0.0155);
MVP		0.82
MPC		0.085
ClinPred		0.76	D
GERP RS		-0.21
Varity_R		0.29
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5719617;