Genetic Variant TRIM65:c.511-91A>G (chr17-75892591-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_173547.4(TRIM65):c.511-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,322,824 control chromosomes in the GnomAD database, including 29,428 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 0.26 ( 6678 hom., cov: 33)

Exomes 𝑓: 0.19 ( 22750 hom. )

Consequence

TRIM65
NM_173547.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.698

Publications

39 publications found

Variant links:

Genes affected

TRIM65 (HGNC:27316): (tripartite motif containing 65) Predicted to enable zinc ion binding activity. Involved in positive regulation of autophagy. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM65 links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173547.4. 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
	TRIM65	NM_173547.4	MANE Select	c.511-91A>G		intron	N/A	NP_775818.2
	TRIM65	NM_001256124.2		c.511-91A>G		intron	N/A	NP_001243053.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRIM65	ENST00000269383.8	TSL:1 MANE Select	c.511-91A>G	intron	N/A	ENSP00000269383.3
TRIM65	ENST00000540812.1	TSL:2	n.377A>G	non_coding_transcript_exon	Exon 2 of 2
TRIM65	ENST00000543309.5	TSL:2	c.130-91A>G	intron	N/A	ENSP00000441480.1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39914

AN:

151996

Hom.:

6652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.188

AC:

219614

AN:

1170710

Hom.:

22750

Cov.:

AF XY:

0.188

AC XY:

109532

AN XY:

583020

show subpopulations

African (AFR)

AF:

0.488

AC:

13354

AN:

27392

American (AMR)

AF:

0.176

AC:

5694

AN:

32262

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

3984

AN:

20166

East Asian (EAS)

AF:

0.138

AC:

5139

AN:

37200

South Asian (SAS)

AF:

0.187

AC:

13088

AN:

70010

European-Finnish (FIN)

AF:

0.121

AC:

5488

AN:

45500

Middle Eastern (MID)

AF:

0.261

AC:

1010

AN:

3872

European-Non Finnish (NFE)

AF:

0.183

AC:

161488

AN:

884414

Other (OTH)

AF:

0.208

AC:

10369

AN:

49894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

9103

18206

27310

36413

45516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5518

11036

16554

22072

27590

<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:

0.263

AC:

39995

AN:

152114

Hom.:

6678

Cov.:

AF XY:

0.257

AC XY:

19129

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.474

AC:

19649

AN:

41494

American (AMR)

AF:

0.205

AC:

3134

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

704

AN:

3466

East Asian (EAS)

AF:

0.132

AC:

683

AN:

5160

South Asian (SAS)

AF:

0.185

AC:

895

AN:

4826

European-Finnish (FIN)

AF:

0.109

AC:

1161

AN:

10604

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

13002

AN:

67964

Other (OTH)

AF:

0.275

AC:

582

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1434

2868

4301

5735

7169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.235

Hom.:

654

Bravo

AF:

0.280

Asia WGS

AF:

0.193

AC:

671

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

(source)

DANN

Benign

0.35

PhyloP100

-0.70

PromoterAI

-0.0044

Neutral

(source)

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

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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