chr17-75891189-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_173547.4(TRIM65):​c.1144G>A​(p.Gly382Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00073 in 1,611,370 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 2 hom. )

Consequence

TRIM65
NM_173547.4 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Publications

2 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.86
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM65NM_173547.4 linkc.1144G>A p.Gly382Arg missense_variant Exon 6 of 6 ENST00000269383.8 NP_775818.2 Q6PJ69

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM65ENST00000269383.8 linkc.1144G>A p.Gly382Arg missense_variant Exon 6 of 6 1 NM_173547.4 ENSP00000269383.3 Q6PJ69

Frequencies

GnomAD3 genomes
AF:
0.000519
AC:
79
AN:
152078
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000942
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.000959
GnomAD2 exomes
AF:
0.000377
AC:
92
AN:
244210
AF XY:
0.000330
show subpopulations
Gnomad AFR exome
AF:
0.00134
Gnomad AMR exome
AF:
0.000464
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000504
Gnomad NFE exome
AF:
0.000475
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000752
AC:
1098
AN:
1459176
Hom.:
2
Cov.:
33
AF XY:
0.000689
AC XY:
500
AN XY:
726068
show subpopulations
African (AFR)
AF:
0.00102
AC:
34
AN:
33478
American (AMR)
AF:
0.000335
AC:
15
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86256
European-Finnish (FIN)
AF:
0.0000787
AC:
4
AN:
50812
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000925
AC:
1029
AN:
1111958
Other (OTH)
AF:
0.000249
AC:
15
AN:
60358
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
78
156
233
311
389
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
42
84
126
168
210
<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:
0.000519
AC:
79
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.000537
AC XY:
40
AN XY:
74420
show subpopulations
African (AFR)
AF:
0.000939
AC:
39
AN:
41528
American (AMR)
AF:
0.000131
AC:
2
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5164
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.000485
AC:
33
AN:
67994
Other (OTH)
AF:
0.000950
AC:
2
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
5
10
15
20
25
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000704
Hom.:
2
Bravo
AF:
0.000563
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000455
AC:
2
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000289
AC:
35
EpiCase
AF:
0.000600
EpiControl
AF:
0.000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1144G>A (p.G382R) alteration is located in exon 6 (coding exon 6) of the TRIM65 gene. This alteration results from a G to A substitution at nucleotide position 1144, causing the glycine (G) at amino acid position 382 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.083
T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.3
H
PhyloP100
5.6
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-7.1
D
REVEL
Pathogenic
0.72
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.76
MutPred
0.85
Gain of MoRF binding (P = 0.0563);
MVP
0.93
MPC
0.78
ClinPred
0.66
D
GERP RS
5.3
Varity_R
0.67
gMVP
0.73
Mutation Taster
=47/53
disease causing

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

Other links and lift over

dbSNP: rs202175254; hg19: chr17-73887270; API