Genetic Variant NM_030912.3: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:

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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

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NM_030912.3:c.571-189A>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