rs73404240

Variant names:

• chr11-5708583-C-A
• rs73404240
• NM_006074.5:c.881C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-5708583-C-A
• chr11-5708583-C-G
• chr11-5708583-C-T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006074.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	NM_006074.5	MANE Select	c.881C>A	p.Thr294Lys	missense	Exon 7 of 8	NP_006065.2
	TRIM22	NM_001199573.2		c.869C>A	p.Thr290Lys	missense	Exon 7 of 8	NP_001186502.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	ENST00000379965.8	TSL:1 MANE Select	c.881C>A	p.Thr294Lys	missense	Exon 7 of 8	ENSP00000369299.3
	TRIM5	ENST00000412903.1	TSL:1	c.-61-28345G>T		intron	N/A	ENSP00000388031.1
	TRIM22	ENST00000901728.1		c.881C>A	p.Thr294Lys	missense	Exon 7 of 8	ENSP00000571787.1

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

GnomAD2 exomes AF: 0.00528 AC: 1265 AN: 239808 AF XY: 0.00408

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 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

African (AFR) AF: 0.0675 AC: 2199 AN: 32594

American (AMR) AF: 0.00360 AC: 151 AN: 41936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25694

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.000178 AC: 15 AN: 84226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00158 AC: 9 AN: 5712

European-Non Finnish (NFE) AF: 0.000149 AC: 165 AN: 1109594

Other (OTH) AF: 0.00423 AC: 254 AN: 59994

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

African (AFR) AF: 0.0742 AC: 3081 AN: 41512

American (AMR) AF: 0.00583 AC: 89 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68028

Other (OTH) AF: 0.0142 AC: 30 AN: 2108

Alfa AF: 0.00505 Hom.: 42

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 v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		-4.1
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.039
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Polyphen		0.024	B
Vest4		0.24
MVP		0.35
MPC		0.061
ClinPred		0.0065	T
GERP RS		-6.6
PromoterAI		0.030	Neutral
Varity_R		0.097
gMVP		0.096
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73404240; hg19: chr11-5729813;