11-5698605-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006074.5(TRIM22):c.750+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,358,996 control chromosomes in the GnomAD database, including 118,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (10551 hom., cov: 32)
  • Exomes 𝑓: 0.42 (108295 hom.)
• Consequence: TRIM22 NM_006074.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.264

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-5698605-T-C is Benign according to our data. Variant chr11-5698605-T-C is described in ClinVar as [Benign]. Clinvar id is 2688019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.750+60T>C		intron_variant		ENST00000379965.8
TRIM22	NM_001199573.2	c.738+60T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.750+60T>C		intron_variant		1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52044 AN: 151956 Hom.: 10548 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.419 AC: 505398 AN: 1206922 Hom.: 108295 AF XY: 0.418 AC XY: 250293 AN XY: 598456

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.342 AC: 52049 AN: 152074 Hom.: 10551 Cov.: 32 AF XY: 0.350 AC XY: 25986 AN XY: 74310

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.357

Alfa AF: 0.388 Hom.: 14242

Bravo AF: 0.336

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.2
Dann	Benign	0.67

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: rs2291844; hg19: chr11-5719835; COSMIC: COSV66090649; COSMIC: COSV66090649;