NM_006074.5:c.463G>A

Variant names:

• chr11-5697287-G-A
• rs7935564
• NM_006074.5:c.463G>A

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.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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 62 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 (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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006074.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	NM_006074.5	MANE Select	c.463G>A	p.Asp155Asn	missense	Exon 3 of 8	NP_006065.2	Q8IYM9-1
	TRIM22	NM_001199573.2		c.463G>A	p.Asp155Asn	missense	Exon 3 of 8	NP_001186502.1	Q8IYM9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM22	ENST00000379965.8	TSL:1 MANE Select	c.463G>A	p.Asp155Asn	missense	Exon 3 of 8	ENSP00000369299.3	Q8IYM9-1
	TRIM5	ENST00000412903.1	TSL:1	c.-61-17049C>T		intron	N/A	ENSP00000388031.1	E7EQQ5
	TRIM22	ENST00000901728.1		c.463G>A	p.Asp155Asn	missense	Exon 3 of 8	ENSP00000571787.1

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

GnomAD2 exomes AF: 0.523 AC: 128878 AN: 246474 AF XY: 0.530

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 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

African (AFR) AF: 0.490 AC: 16352 AN: 33350

American (AMR) AF: 0.413 AC: 18292 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 16568 AN: 26078

East Asian (EAS) AF: 0.197 AC: 7809 AN: 39662

South Asian (SAS) AF: 0.514 AC: 44116 AN: 85862

European-Finnish (FIN) AF: 0.587 AC: 31303 AN: 53304

Middle Eastern (MID) AF: 0.604 AC: 3478 AN: 5760

European-Non Finnish (NFE) AF: 0.599 AC: 665339 AN: 1110286

Other (OTH) AF: 0.561 AC: 33820 AN: 60292

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

African (AFR) AF: 0.489 AC: 20278 AN: 41482

American (AMR) AF: 0.519 AC: 7937 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3468

East Asian (EAS) AF: 0.173 AC: 894 AN: 5174

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.585 AC: 6185 AN: 10576

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.597 AC: 40558 AN: 67956

Other (OTH) AF: 0.542 AC: 1142 AN: 2108

Alfa AF: 0.575 Hom.: 127403

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0000078	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.065
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.033	D
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7935564; hg19: chr11-5718517; COSMIC: COSV101181221; COSMIC: COSV101181221;