11-5697287-G-A

Position:

• chr11-5697287-G-A

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.463G>A​(p.Asp155Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,610,936 control chromosomes in the GnomAD database, including 268,239 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (22830 hom., cov: 33)
  • Exomes 𝑓: 0.57 (245409 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.90

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 (MetaRNN=7.747179E-6).
• BP6: Variant 11-5697287-G-A is Benign according to our data. Variant chr11-5697287-G-A is described in ClinVar as [Benign]. Clinvar id is 2687980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM22	NM_006074.5	c.463G>A	p.Asp155Asn	missense_variant	3/8	ENST00000379965.8	NP_006065.2
TRIM22	NM_001199573.2	c.463G>A	p.Asp155Asn	missense_variant	3/8		NP_001186502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM22	ENST00000379965.8	c.463G>A	p.Asp155Asn	missense_variant	3/8	1	NM_006074.5	ENSP00000369299	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82245 AN: 151946 Hom.: 22819 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.542

GnomAD3 exomes AF: 0.523 AC: 128878 AN: 246474 Hom.: 35861 AF XY: 0.530 AC XY: 70945 AN XY: 133750

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.514

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.601

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.574 AC: 837077 AN: 1458872 Hom.: 245409 Cov.: 43 AF XY: 0.573 AC XY: 415624 AN XY: 725628

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.635

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.541 AC: 82303 AN: 152064 Hom.: 22830 Cov.: 33 AF XY: 0.536 AC XY: 39821 AN XY: 74350

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.542

Alfa AF: 0.581 Hom.: 67331

Bravo AF: 0.531

TwinsUK AF: 0.606 AC: 2246

ALSPAC AF: 0.599 AC: 2309

ESP6500AA AF: 0.498 AC: 1890

ESP6500EA AF: 0.597 AC: 4965

ExAC AF: 0.528 AC: 63790

Asia WGS AF: 0.392 AC: 1363 AN: 3478

EpiCase AF: 0.597

EpiControl AF: 0.608

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.97
DEOGEN2	Benign	0.00066	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T;T;T
MetaRNN	Benign	0.0000077	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.31	N;N;N
REVEL	Benign	0.065
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.033	D;T;T
Polyphen		0.14	B;.;.
Vest4		0.035
MPC		0.057
ClinPred		0.0080	T
GERP RS		-4.5
Varity_R		0.027
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7935564; hg19: chr11-5718517; COSMIC: COSV101181221; COSMIC: COSV101181221;