Variant 4-165040729-C-A 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.657C>A(p.Asn219Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

TRIM60
NM_152620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.102

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=0.124444395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRIM60	NM_152620.3 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	3/3	ENST00000512596.6
TRIM60	NM_001258025.2 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	4/4
TRIM60	XM_011531683.3 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRIM60	ENST00000512596.6 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	3/3	2	NM_152620.3	P1
TRIM60	ENST00000508504.1 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	3/3	1		P1
TRIM60	ENST00000341062.6 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	2/2	5		P1
TRIM60	ENST00000647760.1 linkuse as main transcript	c.657C>A	p.Asn219Lys	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250728

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135704

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:

0.0000793

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727170

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:

0.0000863

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 13, 2021

The c.657C>A (p.N219K) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a C to A substitution at nucleotide position 657, causing the asparagine (N) at amino acid position 219 to be replaced by a lysine (K). 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

0.30

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.055

T;T;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.017

M_CAP

Benign

0.0023

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.48

Polyphen

0.70

P;P;P;P

Vest4

0.18, 0.19

MutPred

0.42

Gain of ubiquitination at N219 (P = 0.0146);Gain of ubiquitination at N219 (P = 0.0146);Gain of ubiquitination at N219 (P = 0.0146);Gain of ubiquitination at N219 (P = 0.0146);

MVP

0.34

MPC

0.057

ClinPred

0.37

GERP RS

1.1

Varity_R

0.10

gMVP

0.17

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