Genetic Variant NM_030912.3:c.667-128C>A (chr10-102654952-C-A) – 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.667-128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,140,794 control chromosomes in the GnomAD database, including 54,852 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 0.30 ( 6871 hom., cov: 32)

Exomes 𝑓: 0.31 ( 47981 hom. )

Consequence

TRIM8
NM_030912.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190

Publications

7 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM8	NM_030912.3 link	c.667-128C>A		intron_variant	Intron 2 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.667-128C>A		intron_variant	Intron 2 of 5		NM_030912.3	ENSP00000496301.1		Q9BZR9

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45525

AN:

151968

Hom.:

6869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.308

AC:

304569

AN:

988708

Hom.:

47981

Cov.:

AF XY:

0.311

AC XY:

156801

AN XY:

504396

show subpopulations

African (AFR)

AF:

0.296

AC:

6684

AN:

22612

American (AMR)

AF:

0.226

AC:

6667

AN:

29494

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

9680

AN:

21754

East Asian (EAS)

AF:

0.296

AC:

10103

AN:

34082

South Asian (SAS)

AF:

0.377

AC:

26608

AN:

70524

European-Finnish (FIN)

AF:

0.229

AC:

11165

AN:

48718

Middle Eastern (MID)

AF:

0.336

AC:

1340

AN:

3990

European-Non Finnish (NFE)

AF:

0.306

AC:

218198

AN:

713174

Other (OTH)

AF:

0.318

AC:

14124

AN:

44360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11141

22282

33424

44565

55706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6064

12128

18192

24256

30320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.300

AC:

45559

AN:

152086

Hom.:

6871

Cov.:

AF XY:

0.299

AC XY:

22190

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.295

AC:

12249

AN:

41480

American (AMR)

AF:

0.279

AC:

4268

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1513

AN:

3472

East Asian (EAS)

AF:

0.316

AC:

1632

AN:

5160

South Asian (SAS)

AF:

0.383

AC:

1844

AN:

4818

European-Finnish (FIN)

AF:

0.227

AC:

2404

AN:

10574

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20379

AN:

67976

Other (OTH)

AF:

0.321

AC:

677

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1638

3275

4913

6550

8188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

774

Bravo

AF:

0.298

Asia WGS

AF:

0.345

AC:

1204

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

(source)

DANN

Benign

0.74

PhyloP100

-0.019

PromoterAI

-0.0038

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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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