11-5698558-A-G

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+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,600,324 control chromosomes in the GnomAD database, including 19,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2815 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17076 hom.)
• Consequence: TRIM22 NM_006074.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162

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 11-5698558-A-G is Benign according to our data. Variant chr11-5698558-A-G is described in ClinVar as [Benign]. Clinvar id is 2688343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.750+13A>G		intron_variant		ENST00000379965.8
TRIM22	NM_001199573.2	c.738+13A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.750+13A>G		intron_variant		1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27038 AN: 151956 Hom.: 2813 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.129 AC: 30822 AN: 238326 Hom.: 2485 AF XY: 0.125 AC XY: 16123 AN XY: 129134

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.0771

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.000402

Gnomad SAS exome AF: 0.0455

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.147 AC: 212178 AN: 1448250 Hom.: 17076 Cov.: 31 AF XY: 0.143 AC XY: 102806 AN XY: 719310

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.0816

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.0478

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.178 AC: 27052 AN: 152074 Hom.: 2815 Cov.: 32 AF XY: 0.173 AC XY: 12852 AN XY: 74370

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.156

Alfa AF: 0.164 Hom.: 587

Bravo AF: 0.180

Asia WGS AF: 0.0370 AC: 132 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 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.2
Dann	Benign	0.79

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: rs11038753; hg19: chr11-5719788;