11-5708350-T-C

Variant names:

• chr11-5708350-T-C
• rs2291845
• NM_006074.5:c.874+77T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TRIM22	NM_006074.5	c.874+77T>C		intron_variant	Intron 6 of 7	ENST00000379965.8	NP_006065.2
TRIM22	NM_001199573.2	c.862+77T>C		intron_variant	Intron 6 of 7		NP_001186502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM22	ENST00000379965.8	c.874+77T>C		intron_variant	Intron 6 of 7	1	NM_006074.5	ENSP00000369299.3

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

African (AFR) AF: 0.0534 AC: 1478 AN: 27700

American (AMR) AF: 0.131 AC: 5370 AN: 41146

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 6918 AN: 23918

East Asian (EAS) AF: 0.0665 AC: 2512 AN: 37788

South Asian (SAS) AF: 0.185 AC: 14644 AN: 79144

European-Finnish (FIN) AF: 0.304 AC: 15282 AN: 50200

Middle Eastern (MID) AF: 0.220 AC: 1159 AN: 5258

European-Non Finnish (NFE) AF: 0.329 AC: 301372 AN: 916394

Other (OTH) AF: 0.263 AC: 13879 AN: 52696

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

African (AFR) AF: 0.0595 AC: 2469 AN: 41496

American (AMR) AF: 0.182 AC: 2777 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3462

East Asian (EAS) AF: 0.0509 AC: 263 AN: 5170

South Asian (SAS) AF: 0.193 AC: 931 AN: 4814

European-Finnish (FIN) AF: 0.301 AC: 3176 AN: 10558

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21702 AN: 67920

Other (OTH) AF: 0.213 AC: 447 AN: 2102

Alfa AF: 0.291 Hom.: 13350

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.20
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291845; hg19: chr11-5729580;