11-5696479-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006074.5(TRIM22):c.247G>A(p.Glu83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 1,614,258 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: TRIM22 NM_006074.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: 0.324

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055968165).
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM22	NM_006074.5	c.247G>A	p.Glu83Lys	missense_variant	2/8	ENST00000379965.8
TRIM22	NM_001199573.2	c.247G>A	p.Glu83Lys	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM22	ENST00000379965.8	c.247G>A	p.Glu83Lys	missense_variant	2/8	1	NM_006074.5	P1

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000859 AC: 215 AN: 250272 Hom.: 0 AF XY: 0.000906 AC XY: 123 AN XY: 135730

Gnomad AFR exome AF: 0.00335

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00923

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000519 AC: 759 AN: 1461892 Hom.: 0 Cov.: 29 AF XY: 0.000540 AC XY: 393 AN XY: 727246

Gnomad4 AFR exome AF: 0.00323

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152366 Hom.: 2 Cov.: 33 AF XY: 0.00197 AC XY: 147 AN XY: 74506

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000764 Hom.: 1

Bravo AF: 0.00172

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00208 AC: 9

ESP6500EA AF: 0.000699 AC: 6

ExAC AF: 0.000726 AC: 88

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.073	N
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.0056	T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.7	L;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.19
Sift	Benign	0.042	D;T;D;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.30	B;.;B;.
Vest4		0.14
MVP		0.71
MPC		0.079
ClinPred		0.0036	T
GERP RS		1.5
Varity_R		0.20
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200668710; hg19: chr11-5717709; COSMIC: COSV99060904; COSMIC: COSV99060904;