11-5698618-C-T

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+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,255,562 control chromosomes in the GnomAD database, including 245,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (38071 hom., cov: 32)
  • Exomes 𝑓: 0.61 (207814 hom.)
• Consequence: TRIM22 NM_006074.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.82

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=-0.89).
• BP6: Variant 11-5698618-C-T is Benign according to our data. Variant chr11-5698618-C-T is described in ClinVar as [Benign]. Clinvar id is 2687999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.750+73C>T		intron_variant		ENST00000379965.8
TRIM22	NM_001199573.2	c.738+73C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.750+73C>T		intron_variant		1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105037 AN: 152046 Hom.: 38019 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.608 AC: 670602 AN: 1103398 Hom.: 207814 AF XY: 0.610 AC XY: 335710 AN XY: 549928

Gnomad4 AFR exome AF: 0.905

Gnomad4 AMR exome AF: 0.714

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.895

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.691 AC: 105147 AN: 152164 Hom.: 38071 Cov.: 32 AF XY: 0.698 AC XY: 51892 AN XY: 74386

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.676

Alfa AF: 0.603 Hom.: 27863

Bravo AF: 0.704

Asia WGS AF: 0.786 AC: 2734 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 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0090
Dann	Benign	0.68

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: rs7950912; hg19: chr11-5719848;