Genetic Variant NM_018073.8:c.523-146A>G (chr11-4602558-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018073.8(TRIM68):c.523-146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,076,770 control chromosomes in the GnomAD database, including 163,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18858 hom., cov: 32)

Exomes 𝑓: 0.55 ( 144970 hom. )

Consequence

TRIM68
NM_018073.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

3 publications found

Variant links:

Genes affected

TRIM68 (HGNC:21161): (tripartite motif containing 68) This gene encodes a member of the tripartite motif-containing protein family, whose members are characterized by a "really interesting new gene" (RING) finger domain, a zinc-binding B-box motif, and a coiled-coil region. Members of this family function as E3 ubiquitin ligases and are involved in a broad range of biological processes. This gene regulates the activation of nuclear receptors, such as androgen receptor, and has been implicated in development of prostate cancer cells, where its expression increases in response to a downregulation of microRNAs. In addition, this gene participates in viral defense regulation as a negative regulator of interferon-beta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

TRIM68 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM68	NM_018073.8 link	c.523-146A>G		intron_variant	Intron 3 of 6	ENST00000300747.10	NP_060543.5	Q6AZZ1-1
TRIM68	NM_001304496.2 link	c.-147-146A>G		intron_variant	Intron 2 of 5		NP_001291425.1	Q6AZZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM68	ENST00000300747.10 link	c.523-146A>G		intron_variant	Intron 3 of 6	1	NM_018073.8	ENSP00000300747.5		Q6AZZ1-1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72854

AN:

151910

Hom.:

18858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.495

GnomAD4 exome

AF:

0.555

AC:

513120

AN:

924742

Hom.:

144970

AF XY:

0.558

AC XY:

257501

AN XY:

461516

show subpopulations

African (AFR)

AF:

0.241

AC:

5196

AN:

21598

American (AMR)

AF:

0.577

AC:

12789

AN:

22148

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

9339

AN:

17132

East Asian (EAS)

AF:

0.647

AC:

21566

AN:

33316

South Asian (SAS)

AF:

0.613

AC:

33772

AN:

55112

European-Finnish (FIN)

AF:

0.598

AC:

19851

AN:

33192

Middle Eastern (MID)

AF:

0.557

AC:

1607

AN:

2884

European-Non Finnish (NFE)

AF:

0.554

AC:

386704

AN:

697722

Other (OTH)

AF:

0.535

AC:

22296

AN:

41638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11481

22962

34444

45925

57406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9604

19208

28812

38416

48020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.479

AC:

72857

AN:

152028

Hom.:

18858

Cov.:

AF XY:

0.488

AC XY:

36269

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.262

AC:

10864

AN:

41478

American (AMR)

AF:

0.566

AC:

8634

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

1851

AN:

3472

East Asian (EAS)

AF:

0.593

AC:

3051

AN:

5148

South Asian (SAS)

AF:

0.600

AC:

2892

AN:

4822

European-Finnish (FIN)

AF:

0.601

AC:

6339

AN:

10552

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.554

AC:

37630

AN:

67982

Other (OTH)

AF:

0.492

AC:

1040

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

668

1336

2004

2672

3340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.529

Hom.:

81175

Bravo

AF:

0.464

Asia WGS

AF:

0.577

AC:

2004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.3

(source)

DANN

Benign

0.69

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over