dbSNP rs1048635: TRIM45:c.*69C>T (chr1-117112236-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025188.4(TRIM45):c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,406,222 control chromosomes in the GnomAD database, including 1,980 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 0.049 ( 215 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1765 hom. )

Consequence

TRIM45
NM_025188.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.843

Publications

4 publications found

Variant links:

Genes affected

TRIM45 (HGNC:19018): (tripartite motif containing 45) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within bone development. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM45 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025188.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM45	NM_025188.4	MANE Select	c.*69C>T		3_prime_UTR	Exon 6 of 6	NP_079464.2
	TRIM45	NM_001145635.2		c.*69C>T		3_prime_UTR	Exon 6 of 6	NP_001139107.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRIM45	ENST00000256649.9	TSL:1 MANE Select	c.*69C>T	3_prime_UTR	Exon 6 of 6	ENSP00000256649.4
TRIM45	ENST00000369464.7	TSL:1	c.*69C>T	3_prime_UTR	Exon 6 of 6	ENSP00000358476.3
TRIM45	ENST00000497970.5	TSL:5	n.*69C>T	non_coding_transcript_exon	Exon 3 of 4	ENSP00000431261.1

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7421

AN:

152158

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.0737

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0553

Gnomad OTH

AF:

0.0544

GnomAD4 exome

AF:

0.0524

AC:

65718

AN:

1253946

Hom.:

1765

Cov.:

AF XY:

0.0529

AC XY:

32324

AN XY:

611184

show subpopulations

African (AFR)

AF:

0.0338

AC:

914

AN:

27076

American (AMR)

AF:

0.0347

AC:

787

AN:

22682

Ashkenazi Jewish (ASJ)

AF:

0.0437

AC:

765

AN:

17502

East Asian (EAS)

AF:

0.0636

AC:

2139

AN:

33652

South Asian (SAS)

AF:

0.0711

AC:

3495

AN:

49154

European-Finnish (FIN)

AF:

0.0245

AC:

1115

AN:

45476

Middle Eastern (MID)

AF:

0.0463

AC:

206

AN:

4450

European-Non Finnish (NFE)

AF:

0.0533

AC:

53445

AN:

1003078

Other (OTH)

AF:

0.0561

AC:

2852

AN:

50876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3076

6152

9227

12303

15379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2228

4456

6684

8912

11140

<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:

0.0488

AC:

7435

AN:

152276

Hom.:

215

Cov.:

AF XY:

0.0481

AC XY:

3579

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0372

AC:

1545

AN:

41560

American (AMR)

AF:

0.0516

AC:

790

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

130

AN:

3472

East Asian (EAS)

AF:

0.0733

AC:

380

AN:

5186

South Asian (SAS)

AF:

0.0749

AC:

361

AN:

4822

European-Finnish (FIN)

AF:

0.0250

AC:

265

AN:

10606

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0553

AC:

3761

AN:

68004

Other (OTH)

AF:

0.0586

AC:

124

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

368

735

1103

1470

1838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0530

Hom.:

375

Bravo

AF:

0.0500

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

(source)

DANN

Benign

0.70

PhyloP100

-0.84

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over