Variant 4-165041316-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152620.3(TRIM60):c.1244T>C(p.Ile415Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,614,130 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 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

TRIM60
NM_152620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4139026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM60	NM_152620.3 linkuse as main transcript	c.1244T>C	p.Ile415Thr	missense_variant	3/3	ENST00000512596.6	NP_689833.1
TRIM60	NM_001258025.2 linkuse as main transcript	c.1244T>C	p.Ile415Thr	missense_variant	4/4		NP_001244954.1
TRIM60	XM_011531683.3 linkuse as main transcript	c.1244T>C	p.Ile415Thr	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.1244T>C	p.Ile415Thr	missense_variant	3/3	2	NM_152620.3	ENSP00000421142	P1
TRIM60	ENST00000508504.1 linkuse as main transcript	c.1244T>C	p.Ile415Thr	missense_variant	3/3	1		ENSP00000426496	P1
TRIM60	ENST00000341062.6 linkuse as main transcript	c.1244T>C	p.Ile415Thr	missense_variant	2/2	5		ENSP00000343765	P1
TRIM60	ENST00000647760.1 linkuse as main transcript	c.1244T>C	p.Ile415Thr	missense_variant	4/4			ENSP00000497401	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251476

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Jan 06, 2023

The c.1244T>C (p.I415T) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a T to C substitution at nucleotide position 1244, causing the isoleucine (I) at amino acid position 415 to be replaced by a threonine (T). 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

Benign

0.32

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.66

.;.;.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.41

T;T;T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.8

H;H;H;H

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.3

.;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

.;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.38, 0.38, 0.38

MVP

0.81

MPC

0.29

ClinPred

0.32

GERP RS

2.5

Varity_R

0.54

gMVP

0.11

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