11-5698315-A-G

Position:

• chr11-5698315-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006074.5(TRIM22):​c.520A>G​(p.Asn174Asp) variant causes a missense, splice region 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. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM22 NM_006074.5 missense, splice_region
• Scores: Splicing: ADA: 0.0002372
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.58

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11655542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM22	NM_006074.5	c.520A>G	p.Asn174Asp	missense_variant, splice_region_variant	4/8	ENST00000379965.8	NP_006065.2
TRIM22	NM_001199573.2	c.520-12A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001186502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM22	ENST00000379965.8	c.520A>G	p.Asn174Asp	missense_variant, splice_region_variant	4/8	1	NM_006074.5	ENSP00000369299	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

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

Feb 17, 2022

The c.520A>G (p.N174D) 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 520, causing the asparagine (N) at amino acid position 174 to be replaced by an aspartic acid (D). 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	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.23
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T;T;T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.10	T;T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.083	B;.;B;.
Vest4		0.14
MutPred		0.38		Loss of MoRF binding (P = 0.0598);Loss of MoRF binding (P = 0.0598);.;Loss of MoRF binding (P = 0.0598);
MVP		0.64
MPC		0.064
ClinPred		0.064	T
GERP RS		-2.0
Varity_R		0.20
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.018
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: rs1853304052; hg19: chr11-5719545;