rs2305120

Variant names:

• chr19-58548362-G-A
• rs2305120
• NM_005762.3:c.1170G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005762.3(TRIM28):​c.1170G>A​(p.Lys390Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,614,062 control chromosomes in the GnomAD database, including 7,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (704 hom., cov: 32)
  • Exomes 𝑓: 0.079 (6380 hom.)
• Consequence: TRIM28 NM_005762.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.126
• Publications: 16 publications found

Genes affected

TRIM28 (HGNC:16384): (tripartite motif containing 28) The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM28 Gene-Disease associations (from GenCC):

• childhood kidney Wilms tumor

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• kidney Wilms tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-58548362-G-A is Benign according to our data. Variant chr19-58548362-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.126 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005762.3. 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
	TRIM28	NM_005762.3	MANE Select	c.1170G>A	p.Lys390Lys	synonymous	Exon 8 of 17	NP_005753.1	Q13263-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM28	ENST00000253024.10	TSL:1 MANE Select	c.1170G>A	p.Lys390Lys	synonymous	Exon 8 of 17	ENSP00000253024.4	Q13263-1
	TRIM28	ENST00000341753.10	TSL:1	c.924G>A	p.Lys308Lys	synonymous	Exon 6 of 15	ENSP00000342232.5	Q13263-2
	TRIM28	ENST00000913378.1		c.1170G>A	p.Lys390Lys	synonymous	Exon 8 of 17	ENSP00000583437.1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12864 AN: 152124 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0793

GnomAD2 exomes AF: 0.105 AC: 26436 AN: 251398 AF XY: 0.104

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.0611

Gnomad EAS exome AF: 0.336

Gnomad FIN exome AF: 0.0818

Gnomad NFE exome AF: 0.0658

Gnomad OTH exome AF: 0.0831

GnomAD4 exome AF: 0.0791 AC: 115616 AN: 1461820 Hom.: 6380 Cov.: 36 AF XY: 0.0802 AC XY: 58325 AN XY: 727210

African (AFR) AF: 0.0799 AC: 2675 AN: 33480

American (AMR) AF: 0.116 AC: 5182 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1588 AN: 26136

East Asian (EAS) AF: 0.317 AC: 12573 AN: 39698

South Asian (SAS) AF: 0.136 AC: 11762 AN: 86256

European-Finnish (FIN) AF: 0.0850 AC: 4538 AN: 53388

Middle Eastern (MID) AF: 0.0537 AC: 310 AN: 5768

European-Non Finnish (NFE) AF: 0.0644 AC: 71623 AN: 1111984

Other (OTH) AF: 0.0888 AC: 5365 AN: 60390

GnomAD4 genome AF: 0.0845 AC: 12872 AN: 152242 Hom.: 704 Cov.: 32 AF XY: 0.0865 AC XY: 6440 AN XY: 74434

African (AFR) AF: 0.0858 AC: 3565 AN: 41542

American (AMR) AF: 0.0850 AC: 1300 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1675 AN: 5180

South Asian (SAS) AF: 0.151 AC: 728 AN: 4828

European-Finnish (FIN) AF: 0.0801 AC: 849 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0635 AC: 4318 AN: 68012

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0741 Hom.: 494

Bravo AF: 0.0847

Asia WGS AF: 0.227 AC: 788 AN: 3478

EpiCase AF: 0.0586

EpiControl AF: 0.0591

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	TRIM28-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.2
DANN	Benign	0.82
PhyloP100		0.13
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs2305120; hg19: chr19-59059729; COSMIC: COSV53398850; COSMIC: COSV53398850;