rs73404240

chr11-5708583-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006074.5(TRIM22):c.881C>A(p.Thr294Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,604,946 control chromosomes in the GnomAD database, including 203 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (88 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.10

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018029511).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.881C>A	p.Thr294Lys	missense_variant	7/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.869C>A	p.Thr290Lys	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.881C>A	p.Thr294Lys	missense_variant	7/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3225 AN: 152098 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00528 AC: 1265 AN: 239808 Hom.: 38 AF XY: 0.00408 AC XY: 531 AN XY: 130130

Gnomad AFR exome AF: 0.0745

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000708

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00225

GnomAD4 exome AF: 0.00192 AC: 2793 AN: 1452730 Hom.: 88 Cov.: 30 AF XY: 0.00170 AC XY: 1231 AN XY: 722526

Gnomad4 AFR exome AF: 0.0675

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000178

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.0212 AC: 3225 AN: 152216 Hom.: 115 Cov.: 32 AF XY: 0.0198 AC XY: 1471 AN XY: 74428

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.00583

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00358 Hom.: 21

Bravo AF: 0.0232

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0668 AC: 249

ESP6500EA AF: 0.000487 AC: 4

ExAC AF: 0.00650 AC: 785

Asia WGS AF: 0.00289 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	0.15
Dann	Benign	0.90
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.69	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.039
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.23	T;T;D
Polyphen		0.024	B;B;.
Vest4		0.24
MVP		0.35
MPC		0.061
ClinPred		0.0065	T
GERP RS		-6.6
Varity_R		0.097
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs73404240; hg19: chr11-5729813;