chr5-181260761-G-C

Variant names:

• chr5-181260761-G-C
• rs754109958
• NM_001346048.2:c.53C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346048.2(TRIM52):​c.53C>G​(p.Ala18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TRIM52 NM_001346048.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31489235).

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.53C>G	p.Ala18Gly	missense	Exon 1 of 2	NP_001332977.1	A0A8I5KQM7
	TRIM52	NM_032765.4		c.53C>G	p.Ala18Gly	missense	Exon 1 of 2	NP_116154.1	Q96A61-1
	TRIM52	NM_001346049.2		c.53C>G	p.Ala18Gly	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.53C>G	p.Ala18Gly	missense	Exon 1 of 2	ENSP00000508553.1	A0A8I5KQM7
	TRIM52	ENST00000611618.1	TSL:1	c.53C>G	p.Ala18Gly	missense	Exon 1 of 2	ENSP00000483005.1	Q96A61-1
	TRIM52	ENST00000503005.2	TSL:5	c.53C>G	p.Ala18Gly	missense	Exon 1 of 2	ENSP00000509065.1	A0A8I5KXQ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250418 AF XY: 0.00000739

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460748 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726630

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111270

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.092
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.55		Loss of sheet (P = 0.1158)
MVP		0.014
ClinPred		0.96	D
GERP RS		3.6
PromoterAI		-0.079	Neutral
Varity_R		0.40
gMVP		0.41
Mutation Taster		=81/19	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: rs754109958; hg19: chr5-180687762;