Genetic Variant TRIM8:c.571-189A>G (chr10-102654464-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030912.3(TRIM8):c.571-189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 582,090 control chromosomes in the GnomAD database, including 25,270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7792 hom., cov: 32)

Exomes 𝑓: 0.27 ( 17478 hom. )

Consequence

TRIM8
NM_030912.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.996

Publications

66 publications found

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 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis and neurodevelopmental syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRIM8 links:

LOC105378460 (HGNC:):

LOC105378460 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM8	NM_030912.3 link	c.571-189A>G		intron_variant	Intron 1 of 5	ENST00000643721.2	NP_112174.2	Q9BZR9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM8	ENST00000643721.2 link	c.571-189A>G		intron_variant	Intron 1 of 5		NM_030912.3	ENSP00000496301.1		Q9BZR9

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47332

AN:

151942

Hom.:

7791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.273

AC:

117611

AN:

430028

Hom.:

17478

Cov.:

AF XY:

0.269

AC XY:

60958

AN XY:

226898

show subpopulations

African (AFR)

AF:

0.382

AC:

4592

AN:

12020

American (AMR)

AF:

0.215

AC:

4144

AN:

19302

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

3757

AN:

12934

East Asian (EAS)

AF:

0.125

AC:

3772

AN:

30276

South Asian (SAS)

AF:

0.148

AC:

5699

AN:

38550

European-Finnish (FIN)

AF:

0.332

AC:

12091

AN:

36424

Middle Eastern (MID)

AF:

0.316

AC:

596

AN:

1888

European-Non Finnish (NFE)

AF:

0.299

AC:

75897

AN:

254068

Other (OTH)

AF:

0.288

AC:

7063

AN:

24566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3876

7752

11627

15503

19379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.311

AC:

47337

AN:

152062

Hom.:

7792

Cov.:

AF XY:

0.307

AC XY:

22839

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.383

AC:

15864

AN:

41456

American (AMR)

AF:

0.250

AC:

3818

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1085

AN:

3466

East Asian (EAS)

AF:

0.178

AC:

919

AN:

5174

South Asian (SAS)

AF:

0.144

AC:

693

AN:

4820

European-Finnish (FIN)

AF:

0.329

AC:

3479

AN:

10576

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20687

AN:

67972

Other (OTH)

AF:

0.293

AC:

619

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1675

3350

5025

6700

8375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.301

Hom.:

28558

Bravo

AF:

0.309

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.60

(source)

DANN

Benign

0.50

PhyloP100

-1.0

PromoterAI

0.023

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-102654464-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over