5-181260347-G-A

Variant names:

• chr5-181260347-G-A
• rs760212623
• NM_001346048.2:c.467C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346048.2(TRIM52):​c.467C>T​(p.Ala156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A156E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM52 NM_001346048.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03213653).

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.467C>T	p.Ala156Val	missense	Exon 1 of 2	NP_001332977.1	A0A8I5KQM7
	TRIM52	NM_032765.4		c.467C>T	p.Ala156Val	missense	Exon 1 of 2	NP_116154.1	Q96A61-1
	TRIM52	NM_001346049.2		c.467C>T	p.Ala156Val	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.467C>T	p.Ala156Val	missense	Exon 1 of 2	ENSP00000508553.1	A0A8I5KQM7
	TRIM52	ENST00000611618.1	TSL:1	c.467C>T	p.Ala156Val	missense	Exon 1 of 2	ENSP00000483005.1	Q96A61-1
	TRIM52	ENST00000503005.2	TSL:5	c.467C>T	p.Ala156Val	missense	Exon 1 of 2	ENSP00000509065.1	A0A8I5KXQ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251494 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.9
DANN	Benign	0.67
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.049
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.17	T
Polyphen		0.012	B
Vest4		0.064
MutPred		0.28		Loss of helix (P = 0.1299)
MVP		0.048
ClinPred		0.016	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.11
Mutation Taster		=98/2	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: rs760212623; hg19: chr5-180687348;