Variant 10-102644640-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_030912.3(TRIM8):c.23G>T(p.Cys8Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,612,882 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

TRIM8
NM_030912.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.03

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]

TRIM8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38838053).

BP6

Variant 10-102644640-G-T is Benign according to our data. Variant chr10-102644640-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2414579.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM8	NM_030912.3 linkuse as main transcript	c.23G>T	p.Cys8Phe	missense_variant	1/6	ENST00000643721.2	NP_112174.2
TRIM8	NM_001345950.1 linkuse as main transcript	c.23G>T	p.Cys8Phe	missense_variant	1/5		NP_001332879.1
TRIM8	NR_144321.1 linkuse as main transcript	n.146G>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIM8	ENST00000643721.2 linkuse as main transcript	c.23G>T	p.Cys8Phe	missense_variant	1/6		NM_030912.3	ENSP00000496301	P1
TRIM8	ENST00000302424.12 linkuse as main transcript	c.23G>T	p.Cys8Phe	missense_variant	1/5	1		ENSP00000302120
TRIM8	ENST00000710327.1 linkuse as main transcript	c.23G>T	p.Cys8Phe	missense_variant	1/6			ENSP00000518207	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000767

AC:

AN:

247646

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134870

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:

0.000186

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

277

AN:

1460746

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

146

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000114

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.0056

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.085

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.7

.;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0060

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;.

Vest4

0.76

MVP

0.082

MPC

2.5

ClinPred

0.36

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.84

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