Genetic Variant NM_001012414.3:c.526-2087T>C (chr4-164957183-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012414.3(TRIM61):c.526-2087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,612,466 control chromosomes in the GnomAD database, including 32,044 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 0.16 ( 2804 hom., cov: 32)

Exomes 𝑓: 0.18 ( 29240 hom. )

Consequence

TRIM61
NM_001012414.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

38 publications found

Variant links:

Genes affected

TRIM61 (HGNC:24339): (tripartite motif containing 61) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM61 links:

FAM218A (HGNC:26466): (family with sequence similarity 218 member A)

FAM218A 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 (MetaRNN=7.5631556E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM61	NM_001012414.3 link	c.526-2087T>C		intron_variant	Intron 3 of 4	ENST00000329314.6	NP_001012414.1	Q5EBN2
FAM218A	NR_160935.1 link	n.236A>G		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM61	ENST00000329314.6 link	c.526-2087T>C		intron_variant	Intron 3 of 4	1	NM_001012414.3	ENSP00000332288.5		Q5EBN2
FAM218A	ENST00000648094.2 link	n.238A>G		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24233

AN:

152016

Hom.:

2801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.219

AC:

54324

AN:

247604

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.0791

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.179

AC:

261179

AN:

1460332

Hom.:

29240

Cov.:

AF XY:

0.184

AC XY:

133513

AN XY:

726338

show subpopulations

African (AFR)

AF:

0.0772

AC:

2583

AN:

33464

American (AMR)

AF:

0.221

AC:

9825

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

5216

AN:

26128

East Asian (EAS)

AF:

0.596

AC:

23603

AN:

39618

South Asian (SAS)

AF:

0.335

AC:

28846

AN:

86038

European-Finnish (FIN)

AF:

0.156

AC:

8314

AN:

53184

Middle Eastern (MID)

AF:

0.256

AC:

1474

AN:

5762

European-Non Finnish (NFE)

AF:

0.152

AC:

169132

AN:

1111386

Other (OTH)

AF:

0.202

AC:

12186

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13244

26488

39732

52976

66220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6312

12624

18936

25248

31560

<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:

0.159

AC:

24245

AN:

152134

Hom.:

2804

Cov.:

AF XY:

0.164

AC XY:

12228

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0802

AC:

3329

AN:

41518

American (AMR)

AF:

0.171

AC:

2616

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3466

East Asian (EAS)

AF:

0.612

AC:

3155

AN:

5156

South Asian (SAS)

AF:

0.370

AC:

1784

AN:

4816

European-Finnish (FIN)

AF:

0.150

AC:

1585

AN:

10580

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10575

AN:

67992

Other (OTH)

AF:

0.203

AC:

430

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

971

1941

2912

3882

4853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.167

Hom.:

10230

Bravo

AF:

0.160

TwinsUK

AF:

0.148

AC:

547

ALSPAC

AF:

0.142

AC:

549

ESP6500AA

AF:

0.0790

AC:

348

ESP6500EA

AF:

0.151

AC:

1298

ExAC

AF:

0.212

AC:

25701

Asia WGS

AF:

0.495

AC:

1720

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.0

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.045

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000076

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-1.7

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.074

Polyphen

0.048

Vest4

0.011

MPC

0.91

ClinPred

0.0024

GERP RS

-1.1

Varity_R

0.23

gMVP

0.010

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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