dbSNP rs3744028: 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:

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=-0.86).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM65	NM_173547.4 link	c.511-91A>G		intron_variant	Intron 2 of 5	ENST00000269383.8	NP_775818.2	Q6PJ69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM65	ENST00000269383.8 link	c.511-91A>G		intron_variant	Intron 2 of 5	1	NM_173547.4	ENSP00000269383.3		Q6PJ69

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over