Variant 4-165040221-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152620.3(TRIM60):c.149C>T(p.Thr50Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM60
NM_152620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.17

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073802024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM60	NM_152620.3 linkuse as main transcript	c.149C>T	p.Thr50Ile	missense_variant	3/3	ENST00000512596.6	NP_689833.1
TRIM60	NM_001258025.2 linkuse as main transcript	c.149C>T	p.Thr50Ile	missense_variant	4/4		NP_001244954.1
TRIM60	XM_011531683.3 linkuse as main transcript	c.149C>T	p.Thr50Ile	missense_variant	2/2		XP_011529985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM60	ENST00000512596.6 linkuse as main transcript	c.149C>T	p.Thr50Ile	missense_variant	3/3	2	NM_152620.3	ENSP00000421142	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251492

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Nov 17, 2023

The c.149C>T (p.T50I) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a C to T substitution at nucleotide position 149, causing the threonine (T) at amino acid position 50 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.65

DANN

Benign

0.67

DEOGEN2

Benign

0.010

T;T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.018

.;.;T;.;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.074

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;L;.;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

.;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.40

.;T;T;T;T

Sift4G

Benign

0.51

.;T;T;T;T

Polyphen

0.0090

B;B;.;B;B

Vest4

0.040, 0.045, 0.035

MutPred

0.42

Loss of ubiquitination at K45 (P = 0.1264);Loss of ubiquitination at K45 (P = 0.1264);Loss of ubiquitination at K45 (P = 0.1264);Loss of ubiquitination at K45 (P = 0.1264);Loss of ubiquitination at K45 (P = 0.1264);

MVP

0.030

MPC

0.041

ClinPred

0.048

GERP RS

-4.1

Varity_R

0.027

gMVP

0.27

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