Genetic Variant NM_173547.4:c.1312G>A (chr17-75891021-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_173547.4(TRIM65):c.1312G>A(p.Gly438Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 1,607,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

TRIM65
NM_173547.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28738573).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM65	NM_173547.4	MANE Select	c.1312G>A	p.Gly438Arg	missense	Exon 6 of 6	NP_775818.2
	TRIM65	NM_001256124.2		c.1246G>A	p.Gly416Arg	missense	Exon 5 of 5	NP_001243053.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIM65	ENST00000269383.8	TSL:1 MANE Select	c.1312G>A	p.Gly438Arg	missense	Exon 6 of 6	ENSP00000269383.3	Q6PJ69
TRIM65	ENST00000924710.1		c.1351G>A	p.Gly451Arg	missense	Exon 6 of 6	ENSP00000594769.1
TRIM65	ENST00000924711.1		c.1285G>A	p.Gly429Arg	missense	Exon 5 of 5	ENSP00000594770.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000981

AC:

AN:

234372

AF XY:

0.0000938

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000963

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1455534

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

723828

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33274

American (AMR)

AF:

0.000642

AC:

AN:

43596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39230

South Asian (SAS)

AF:

0.00

AC:

AN:

85522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109578

Other (OTH)

AF:

0.0000999

AC:

AN:

60074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000210

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41586

American (AMR)

AF:

0.00163

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.29

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.8

PhyloP100

2.8

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.53

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.49

MutPred

0.54

Loss of sheet (P = 0.0817)

MVP

0.87

MPC

0.79

ClinPred

0.77

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.62

Mutation Taster

=90/10

polymorphism

(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