Genetic Variant TRIM46:p.Thr287Thr (chr1-155177242-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_025058.5(TRIM46):c.861G>A(p.Thr287Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,686 control chromosomes in the GnomAD database, including 127,443 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 0.37 ( 11219 hom., cov: 32)

Exomes 𝑓: 0.39 ( 116224 hom. )

Consequence

TRIM46
NM_025058.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

42 publications found

Variant links:

Genes affected

TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]

TRIM46 links:

ENSG00000273088 (HGNC:):

ENSG00000273088 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM46	NM_025058.5 link	c.861G>A	p.Thr287Thr	synonymous_variant	Exon 5 of 10	ENST00000334634.9	NP_079334.3	Q7Z4K8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM46	ENST00000334634.9 link	c.861G>A	p.Thr287Thr	synonymous_variant	Exon 5 of 10	1	NM_025058.5	ENSP00000334657.4		Q7Z4K8-1
ENSG00000273088	ENST00000473363.3 link	c.49-3768C>T		intron_variant	Intron 1 of 4	5		ENSP00000477381.3		V9GZ38

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56193

AN:

151906

Hom.:

11221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.433

AC:

108881

AN:

251372

AF XY:

0.424

show subpopulations

Gnomad AFR exome

AF:

0.274

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.387

AC:

565986

AN:

1461660

Hom.:

116224

Cov.:

AF XY:

0.386

AC XY:

280778

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.263

AC:

8796

AN:

33478

American (AMR)

AF:

0.590

AC:

26377

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7346

AN:

26136

East Asian (EAS)

AF:

0.799

AC:

31704

AN:

39698

South Asian (SAS)

AF:

0.440

AC:

37939

AN:

86240

European-Finnish (FIN)

AF:

0.459

AC:

24490

AN:

53408

Middle Eastern (MID)

AF:

0.267

AC:

1538

AN:

5768

European-Non Finnish (NFE)

AF:

0.364

AC:

404714

AN:

1111818

Other (OTH)

AF:

0.382

AC:

23082

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

18596

37192

55787

74383

92979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13184

26368

39552

52736

65920

<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:

0.370

AC:

56200

AN:

152026

Hom.:

11219

Cov.:

AF XY:

0.379

AC XY:

28124

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.273

AC:

11309

AN:

41492

American (AMR)

AF:

0.486

AC:

7428

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

962

AN:

3468

East Asian (EAS)

AF:

0.770

AC:

3957

AN:

5136

South Asian (SAS)

AF:

0.438

AC:

2111

AN:

4824

European-Finnish (FIN)

AF:

0.456

AC:

4821

AN:

10568

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24503

AN:

67952

Other (OTH)

AF:

0.361

AC:

761

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1766

3532

5297

7063

8829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.364

Hom.:

48027

Bravo

AF:

0.374

Asia WGS

AF:

0.544

AC:

1890

AN:

3478

EpiCase

AF:

0.326

EpiControl

AF:

0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.94

(source)

DANN

Benign

0.81

PhyloP100

-1.6

Mutation Taster

=95/5

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

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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