rs61735273

chr11-5698526-C-T

Variant summary

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

The NM_006074.5(TRIM22):c.731C>T(p.Ser244Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00801 in 1,613,094 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.042 (464 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (422 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

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=0.0017862618).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.731C>T	p.Ser244Leu	missense_variant	4/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.719C>T	p.Ser240Leu	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.731C>T	p.Ser244Leu	missense_variant	4/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6321 AN: 152078 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0104 AC: 2584 AN: 248336 Hom.: 181 AF XY: 0.00778 AC XY: 1048 AN XY: 134760

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00662

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00451 AC: 6585 AN: 1460898 Hom.: 422 Cov.: 35 AF XY: 0.00380 AC XY: 2764 AN XY: 726664

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.00793

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000280

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0417 AC: 6340 AN: 152196 Hom.: 464 Cov.: 33 AF XY: 0.0404 AC XY: 3005 AN XY: 74416

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0182 Hom.: 119

Bravo AF: 0.0521

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.137 AC: 558

ESP6500EA AF: 0.000595 AC: 5

ExAC AF: 0.0127 AC: 1535

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.093
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.90	D;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	1.0	N;D
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		1.0	D;D
Vest4		0.11
MPC		0.26
ClinPred		0.050	T
GERP RS		3.5
Varity_R		0.35
gMVP		0.084

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: rs61735273; hg19: chr11-5719756; COSMIC: COSV104699697; COSMIC: COSV104699697;