4-165041202-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152620.3(TRIM60):ā€‹c.1130A>Cā€‹(p.Asp377Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 32)
Exomes š‘“: 0.00013 ( 0 hom. )

Consequence

TRIM60
NM_152620.3 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.035501987).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIM60NM_152620.3 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 3/3 ENST00000512596.6
TRIM60NM_001258025.2 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 4/4
TRIM60XM_011531683.3 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIM60ENST00000512596.6 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 3/32 NM_152620.3 P1
TRIM60ENST00000508504.1 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 3/31 P1
TRIM60ENST00000341062.6 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 2/25 P1
TRIM60ENST00000647760.1 linkuse as main transcriptc.1130A>C p.Asp377Ala missense_variant 4/4 P1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000235
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000795
AC:
20
AN:
251448
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135896
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:
0.000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000131
AC:
192
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.000127
AC XY:
92
AN XY:
727246
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:
0.000165
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000235
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsOct 04, 2022The c.1130A>C (p.D377A) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a A to C substitution at nucleotide position 1130, causing the aspartic acid (D) at amino acid position 377 to be replaced by an alanine (A). 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
0.12
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Benign
0.77
DEOGEN2
Benign
0.0051
T;T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.074
N
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.036
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.22
N;N;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
Polyphen
0.013
B;B;B;B
Vest4
0.076, 0.095, 0.081
MVP
0.30
MPC
0.044
ClinPred
0.020
T
GERP RS
1.4
Varity_R
0.062
gMVP
0.032

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.

Other links and lift over

dbSNP: rs144130602; hg19: chr4-165962354; API