chr10-102644659-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_030912.3(TRIM8):ā€‹c.42C>Gā€‹(p.Ile14Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000728 in 1,613,388 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00060 ( 0 hom., cov: 33)
Exomes š‘“: 0.00074 ( 3 hom. )

Consequence

TRIM8
NM_030912.3 missense

Scores

2
3
14

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.411
Variant links:
Genes affected
TRIM8 (HGNC:15579): (tripartite motif containing 8) This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE). [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.096564054).
BP6
Variant 10-102644659-C-G is Benign according to our data. Variant chr10-102644659-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1596826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIM8NM_030912.3 linkuse as main transcriptc.42C>G p.Ile14Met missense_variant 1/6 ENST00000643721.2 NP_112174.2
TRIM8NM_001345950.1 linkuse as main transcriptc.42C>G p.Ile14Met missense_variant 1/5 NP_001332879.1
TRIM8NR_144321.1 linkuse as main transcriptn.165C>G non_coding_transcript_exon_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIM8ENST00000643721.2 linkuse as main transcriptc.42C>G p.Ile14Met missense_variant 1/6 NM_030912.3 ENSP00000496301 P1
TRIM8ENST00000302424.12 linkuse as main transcriptc.42C>G p.Ile14Met missense_variant 1/51 ENSP00000302120
TRIM8ENST00000710327.1 linkuse as main transcriptc.42C>G p.Ile14Met missense_variant 1/6 ENSP00000518207 P1

Frequencies

GnomAD3 genomes
AF:
0.000598
AC:
91
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
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:
0.00110
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000579
AC:
144
AN:
248814
Hom.:
0
AF XY:
0.000644
AC XY:
87
AN XY:
135196
show subpopulations
Gnomad AFR exome
AF:
0.0000630
Gnomad AMR exome
AF:
0.000755
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000979
Gnomad OTH exome
AF:
0.000822
GnomAD4 exome
AF:
0.000741
AC:
1083
AN:
1461102
Hom.:
3
Cov.:
32
AF XY:
0.000729
AC XY:
530
AN XY:
726864
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000902
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000598
AC:
91
AN:
152286
Hom.:
0
Cov.:
33
AF XY:
0.000672
AC XY:
50
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00110
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000759
Hom.:
0
Bravo
AF:
0.000570
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.000429
AC:
52
EpiCase
AF:
0.000709
EpiControl
AF:
0.00136

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
TRIM8-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 07, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 27, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.044
T;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.097
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.70
N;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.15
.;N
REVEL
Benign
0.24
Sift
Benign
0.17
.;T
Sift4G
Uncertain
0.018
.;D
Polyphen
0.99
D;.
Vest4
0.57
MVP
0.23
MPC
1.8
ClinPred
0.057
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.43

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: rs140859541; hg19: chr10-104404416; API