Genetic Variant NM_006074.5:c.209C>A (chr11-5696441-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006074.5(TRIM22):c.209C>A(p.Pro70His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P70T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

TRIM22
NM_006074.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Publications

0 publications found

Variant links:

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]

TRIM22 links:

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]

TRIM5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.209C>A	p.Pro70His	missense	Exon 2 of 8	NP_006065.2	Q8IYM9-1
	TRIM22	NM_001199573.2		c.209C>A	p.Pro70His	missense	Exon 2 of 8	NP_001186502.1	Q8IYM9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM22	ENST00000379965.8	TSL:1 MANE Select	c.209C>A	p.Pro70His	missense	Exon 2 of 8	ENSP00000369299.3	Q8IYM9-1
TRIM5	ENST00000412903.1	TSL:1	c.-61-16203G>T		intron	N/A	ENSP00000388031.1	E7EQQ5
TRIM22	ENST00000901728.1		c.209C>A	p.Pro70His	missense	Exon 2 of 8	ENSP00000571787.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.1

PhyloP100

1.4

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.36

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.013

Polyphen

0.12

Vest4

0.44

MutPred

0.65

Gain of MoRF binding (P = 0.0587)

MVP

0.67

MPC

0.066

ClinPred

0.84

GERP RS

3.9

Varity_R

0.22

gMVP

0.24

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over