Genetic Variant NM_173547.4:c.1405C>A (chr17-75890928-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173547.4(TRIM65):c.1405C>A(p.Pro469Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,553,124 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 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

TRIM65
NM_173547.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09611073).

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.1405C>A	p.Pro469Thr	missense	Exon 6 of 6	NP_775818.2
	TRIM65	NM_001256124.2		c.1339C>A	p.Pro447Thr	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.1405C>A	p.Pro469Thr	missense	Exon 6 of 6	ENSP00000269383.3	Q6PJ69
TRIM65	ENST00000924710.1		c.1444C>A	p.Pro482Thr	missense	Exon 6 of 6	ENSP00000594769.1
TRIM65	ENST00000924711.1		c.1378C>A	p.Pro460Thr	missense	Exon 5 of 5	ENSP00000594770.1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000171

AC:

AN:

158054

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000844

Gnomad ASJ exome

AF:

0.000954

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000110

AC:

154

AN:

1400944

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

691982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31518

American (AMR)

AF:

0.0000577

AC:

AN:

34634

Ashkenazi Jewish (ASJ)

AF:

0.000880

AC:

AN:

25014

East Asian (EAS)

AF:

0.00

AC:

AN:

36030

South Asian (SAS)

AF:

0.00

AC:

AN:

79778

European-Finnish (FIN)

AF:

0.0000605

AC:

AN:

49604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

0.000114

AC:

123

AN:

1080958

Other (OTH)

AF:

0.0000690

AC:

AN:

57988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000269

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000757

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000236

AC:

ExAC

AF:

0.0000956

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

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

M_CAP

Benign

0.053

MetaRNN

Benign

0.096

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.4

PhyloP100

2.7

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.34

Sift

Benign

0.12

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.24

MVP

0.77

MPC

0.76

ClinPred

0.19

GERP RS

5.2

Varity_R

0.41

gMVP

0.38

Mutation Taster

=96/4

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

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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