Variant 10-102644753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030912.3(TRIM8):c.136G>A(p.Asp46Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,900 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM8
NM_030912.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89

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:

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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=0.2939805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRIM8	NM_030912.3 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	1/6	ENST00000643721.2
TRIM8	NM_001345950.1 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	1/5
TRIM8	NR_144321.1 linkuse as main transcript	n.259G>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRIM8	ENST00000643721.2 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	1/6		NM_030912.3	P1
TRIM8	ENST00000302424.12 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	1/5	1
TRIM8	ENST00000710327.1 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	1/6			P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248002

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134812

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:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726788

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 submitter

clinical testing

Ambry Genetics

Mar 07, 2021

The c.136G>A (p.D46N) alteration is located in exon 1 (coding exon 1) of the TRIM8 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.21

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

Polyphen

0.72

P;.

Vest4

0.25

MutPred

0.46

Loss of glycosylation at S47 (P = 0.1254);Loss of glycosylation at S47 (P = 0.1254);

MVP

0.33

MPC

1.6

ClinPred

0.87

GERP RS

3.5

Varity_R

0.15

gMVP

0.48

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