chr10-102644736-G-C

Variant summary

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

The NM_030912.3(TRIM8):ā€‹c.119G>Cā€‹(p.Gly40Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,944 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TRIM8
NM_030912.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
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]

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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=0.26618075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIM8NM_030912.3 linkuse as main transcriptc.119G>C p.Gly40Ala missense_variant 1/6 ENST00000643721.2 NP_112174.2
TRIM8NM_001345950.1 linkuse as main transcriptc.119G>C p.Gly40Ala missense_variant 1/5 NP_001332879.1
TRIM8NR_144321.1 linkuse as main transcriptn.242G>C 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.119G>C p.Gly40Ala missense_variant 1/6 NM_030912.3 ENSP00000496301 P1
TRIM8ENST00000302424.12 linkuse as main transcriptc.119G>C p.Gly40Ala missense_variant 1/51 ENSP00000302120
TRIM8ENST00000710327.1 linkuse as main transcriptc.119G>C p.Gly40Ala missense_variant 1/6 ENSP00000518207 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460944
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726784
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 12, 2024The c.119G>C (p.G40A) alteration is located in exon 1 (coding exon 1) of the TRIM8 gene. This alteration results from a G to C substitution at nucleotide position 119, causing the glycine (G) at amino acid position 40 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
0.11
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
25
DANN
Benign
0.97
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.071
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.82
N;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.5
.;D
REVEL
Benign
0.17
Sift
Benign
0.10
.;T
Sift4G
Benign
0.31
.;T
Polyphen
0.047
B;.
Vest4
0.34
MutPred
0.58
Loss of ubiquitination at K45 (P = 0.1083);Loss of ubiquitination at K45 (P = 0.1083);
MVP
0.23
MPC
1.2
ClinPred
0.80
D
GERP RS
3.9
Varity_R
0.43
gMVP
0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104404493; API