Variant 4-165041319-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152620.3(TRIM60):c.1247G>T(p.Gly416Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TRIM60
NM_152620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

TRIM60 (HGNC:21162): (tripartite motif containing 60) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Pseudogenes of this gene are located on more than six chromosomes including chromosome 4. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

TRIM60 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM60	NM_152620.3 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	3/3	ENST00000512596.6	NP_689833.1
TRIM60	NM_001258025.2 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	4/4		NP_001244954.1
TRIM60	XM_011531683.3 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	2/2		XP_011529985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIM60	ENST00000512596.6 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	3/3	2	NM_152620.3	ENSP00000421142	P1
TRIM60	ENST00000508504.1 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	3/3	1		ENSP00000426496	P1
TRIM60	ENST00000341062.6 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	2/2	5		ENSP00000343765	P1
TRIM60	ENST00000647760.1 linkuse as main transcript	c.1247G>T	p.Gly416Val	missense_variant	4/4			ENSP00000497401	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251472

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1247G>T (p.G416V) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the glycine (G) at amino acid position 416 to be replaced by a valine (V). 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

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

.;.;.;T

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

3.2

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-8.8

.;D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

.;D;D;D

Sift4G

Pathogenic

0.0

.;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.59, 0.59, 0.59

MutPred

0.88

Loss of catalytic residue at I415 (P = 0.0731);Loss of catalytic residue at I415 (P = 0.0731);Loss of catalytic residue at I415 (P = 0.0731);Loss of catalytic residue at I415 (P = 0.0731);

MVP

0.81

MPC

0.30

ClinPred

1.0

GERP RS

2.5

Varity_R

0.80

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over