11-5708350-T-C

Position:

• chr11-5708350-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.874+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,386,248 control chromosomes in the GnomAD database, including 60,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4736 hom., cov: 31)
  • Exomes 𝑓: 0.29 (55927 hom.)
• Consequence: TRIM22 NM_006074.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.195

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=-0.87).
• BP6: Variant 11-5708350-T-C is Benign according to our data. Variant chr11-5708350-T-C is described in ClinVar as [Benign]. Clinvar id is 2688206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM22	NM_006074.5	c.874+77T>C		intron_variant		ENST00000379965.8	NP_006065.2
TRIM22	NM_001199573.2	c.862+77T>C		intron_variant			NP_001186502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM22	ENST00000379965.8	c.874+77T>C		intron_variant		1	NM_006074.5	ENSP00000369299	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33222 AN: 151886 Hom.: 4735 Cov.: 31

Gnomad AFR AF: 0.0597

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.294 AC: 362614 AN: 1234244 Hom.: 55927 Cov.: 17 AF XY: 0.291 AC XY: 181770 AN XY: 623828

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.219 AC: 33215 AN: 152004 Hom.: 4736 Cov.: 31 AF XY: 0.214 AC XY: 15879 AN XY: 74292

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.213

Alfa AF: 0.295 Hom.: 10024

Bravo AF: 0.199

Asia WGS AF: 0.133 AC: 465 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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.70

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: rs2291845; hg19: chr11-5729580;