rs8140207

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039141.3(TRIOBP):c.4116G>T(p.Glu1372Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,612,404 control chromosomes in the GnomAD database, including 72,369 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5412 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66957 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.150

Publications

30 publications found

Variant links:

Genes affected

TRIOBP (HGNC:17009): (TRIO and F-actin binding protein) This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]

TRIOBP Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 28
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

TRIOBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013839304).

BP6

Variant 22-37734452-G-T is Benign according to our data. Variant chr22-37734452-G-T is described in ClinVar as Benign. ClinVar VariationId is 43854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.4116G>T	p.Glu1372Asp	missense	Exon 9 of 24	NP_001034230.1	Q9H2D6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIOBP	ENST00000644935.1	MANE Select	c.4116G>T	p.Glu1372Asp	missense	Exon 9 of 24	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000344404.10	TSL:2	n.*3599G>T		non_coding_transcript_exon	Exon 7 of 22	ENSP00000340312.6	H7BXW4
TRIOBP	ENST00000344404.10	TSL:2	n.*3599G>T		3_prime_UTR	Exon 7 of 22	ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36976

AN:

151976

Hom.:

5416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.268

GnomAD2 exomes

AF:

0.309

AC:

76041

AN:

246442

AF XY:

0.317

show subpopulations

Gnomad AFR exome

AF:

0.0676

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.297

AC:

433559

AN:

1460310

Hom.:

66957

Cov.:

AF XY:

0.301

AC XY:

218701

AN XY:

726408

show subpopulations

African (AFR)

AF:

0.0650

AC:

2176

AN:

33470

American (AMR)

AF:

0.319

AC:

14216

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

9270

AN:

26116

East Asian (EAS)

AF:

0.370

AC:

14671

AN:

39688

South Asian (SAS)

AF:

0.398

AC:

34314

AN:

86170

European-Finnish (FIN)

AF:

0.336

AC:

17652

AN:

52596

Middle Eastern (MID)

AF:

0.349

AC:

2010

AN:

5766

European-Non Finnish (NFE)

AF:

0.289

AC:

321471

AN:

1111566

Other (OTH)

AF:

0.295

AC:

17779

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17558

35116

52675

70233

87791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10568

21136

31704

42272

52840

<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:

0.243

AC:

36977

AN:

152094

Hom.:

5412

Cov.:

AF XY:

0.249

AC XY:

18527

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0728

AC:

3023

AN:

41550

American (AMR)

AF:

0.293

AC:

4473

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1258

AN:

3468

East Asian (EAS)

AF:

0.312

AC:

1611

AN:

5156

South Asian (SAS)

AF:

0.407

AC:

1957

AN:

4814

European-Finnish (FIN)

AF:

0.333

AC:

3517

AN:

10568

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.297

AC:

20158

AN:

67942

Other (OTH)

AF:

0.268

AC:

564

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1384

2768

4152

5536

6920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.284

Hom.:

8342

Bravo

AF:

0.231

TwinsUK

AF:

0.289

AC:

1070

ALSPAC

AF:

0.280

AC:

1078

ESP6500AA

AF:

0.0759

AC:

295

ESP6500EA

AF:

0.295

AC:

2442

ExAC

AF:

0.306

AC:

36967

Asia WGS

AF:

0.355

AC:

1234

AN:

3478

EpiCase

AF:

0.308

EpiControl

AF:

0.310

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.3

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

0.15

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.069

Sift

Benign

0.18

Sift4G

Benign

0.24

Polyphen

0.051

Vest4

0.020

MutPred

0.059

Loss of glycosylation at P1374 (P = 0.0864)

MPC

0.10

ClinPred

0.0039

GERP RS

0.94

Varity_R

0.056

gMVP

0.083

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over