Genetic Variant NM_006778.4:c.194G>A (chr6-30160665-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006778.4(TRIM10):c.194G>A(p.Arg65His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,614,092 control chromosomes in the GnomAD database, including 5,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1328 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3964 hom. )

Consequence

TRIM10
NM_006778.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.870

Publications

32 publications found

Variant links:

Genes affected

TRIM10 (HGNC:10072): (tripartite motif containing 10) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to cytoplasmic bodies. Studies in mice suggest that this protein plays a role in terminal differentiation of erythroid cells. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TRIM10 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 (MetaRNN=0.0015873015).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM10	NM_006778.4 link	c.194G>A	p.Arg65His	missense_variant	Exon 1 of 7	ENST00000449742.7	NP_006769.2	Q9UDY6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM10	ENST00000449742.7 link	c.194G>A	p.Arg65His	missense_variant	Exon 1 of 7	1	NM_006778.4	ENSP00000397073.2		Q9UDY6-1
TRIM10	ENST00000376704.3 link	c.194G>A	p.Arg65His	missense_variant	Exon 1 of 8	1		ENSP00000365894.3		Q9UDY6-2

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16084

AN:

152080

Hom.:

1326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0551

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.0721

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.0663

AC:

16667

AN:

251484

AF XY:

0.0632

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.0724

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0658

AC:

96207

AN:

1461894

Hom.:

3964

Cov.:

AF XY:

0.0644

AC XY:

46831

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.217

AC:

7260

AN:

33480

American (AMR)

AF:

0.0588

AC:

2632

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

1462

AN:

26136

East Asian (EAS)

AF:

0.00214

AC:

AN:

39700

South Asian (SAS)

AF:

0.0258

AC:

2229

AN:

86258

European-Finnish (FIN)

AF:

0.0559

AC:

2988

AN:

53420

Middle Eastern (MID)

AF:

0.149

AC:

857

AN:

5768

European-Non Finnish (NFE)

AF:

0.0669

AC:

74404

AN:

1112012

Other (OTH)

AF:

0.0710

AC:

4290

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6673

13345

20018

26690

33363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2700

5400

8100

10800

13500

<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:

0.106

AC:

16109

AN:

152198

Hom.:

1328

Cov.:

AF XY:

0.102

AC XY:

7558

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.214

AC:

8896

AN:

41500

American (AMR)

AF:

0.0732

AC:

1121

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3470

East Asian (EAS)

AF:

0.00366

AC:

AN:

5188

South Asian (SAS)

AF:

0.0199

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0551

AC:

584

AN:

10608

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0721

AC:

4905

AN:

67984

Other (OTH)

AF:

0.114

AC:

240

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

692

1384

2076

2768

3460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0783

Hom.:

2502

Bravo

AF:

0.113

TwinsUK

AF:

0.0669

AC:

248

ALSPAC

AF:

0.0656

AC:

253

ESP6500AA

AF:

0.211

AC:

928

ESP6500EA

AF:

0.0687

AC:

591

ExAC

AF:

0.0700

AC:

8503

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0772

EpiControl

AF:

0.0788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0040

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.062

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

L;L

PhyloP100

-0.87

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.080

Sift

Benign

0.075

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.014

B;B

Vest4

0.033

MPC

0.13

ClinPred

0.0027

GERP RS

2.6

PromoterAI

-0.063

Neutral

(source)

Varity_R

0.035

gMVP

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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