NM_001346048.2:c.803A>G

Variant names:

• chr5-181260011-T-C
• rs201912827
• NM_001346048.2:c.803A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001346048.2(TRIM52):​c.803A>G​(p.Gln268Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: TRIM52 NM_001346048.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.588
• Publications: 2 publications found

Genes affected

TRIM52 (HGNC:19024): (tripartite motif containing 52) Enables transcription coactivator activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of NF-kappaB transcription factor activity; and protein autoubiquitination. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRIM52-AS1 (HGNC:49006): (TRIM52 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030762196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346048.2. 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
	TRIM52	NM_001346048.2	MANE Select	c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	NP_001332977.1	A0A8I5KQM7
	TRIM52	NM_032765.4		c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	NP_116154.1	Q96A61-1
	TRIM52	NM_001346049.2		c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	NP_001332978.1	A0A8I5KYD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM52	ENST00000688015.1	MANE Select	c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	ENSP00000508553.1	A0A8I5KQM7
	TRIM52	ENST00000611618.1	TSL:1	c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	ENSP00000483005.1	Q96A61-1
	TRIM52	ENST00000503005.2	TSL:5	c.803A>G	p.Gln268Arg	missense	Exon 1 of 2	ENSP00000509065.1	A0A8I5KXQ2

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000139 AC: 35 AN: 251320 AF XY: 0.000169

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000313 AC: 458 AN: 1461552 Hom.: 0 Cov.: 33 AF XY: 0.000315 AC XY: 229 AN XY: 727082

African (AFR) AF: 0.0000896 AC: 3 AN: 33470

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.000397 AC: 441 AN: 1112008

Other (OTH) AF: 0.000116 AC: 7 AN: 60364

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74498

African (AFR) AF: 0.000120 AC: 5 AN: 41590

American (AMR) AF: 0.000458 AC: 7 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000282 Hom.: 0

Bravo AF: 0.000208

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000273

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.59
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.079	T
Polyphen		0.0020	B
Vest4		0.090
MVP		0.067
ClinPred		0.025	T
GERP RS		0.84
Varity_R		0.12
gMVP		0.14
Mutation Taster		=94/6	polymorphism

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: rs201912827; hg19: chr5-180687012;