rs199646135

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_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.265C>G(p.Pro89Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,613,514 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 24 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.411

Publications

8 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:

ENSG00000100101 (HGNC:):

ENSG00000100101 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=0.0034452677).

BP6

Variant 22-37713220-C-G is Benign according to our data. Variant chr22-37713220-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00377 (573/152184) while in subpopulation NFE AF = 0.0061 (415/68002). AF 95% confidence interval is 0.00562. There are 3 homozygotes in GnomAd4. There are 240 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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.265C>G	p.Pro89Ala	missense	Exon 5 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.265C>G	p.Pro89Ala	missense	Exon 5 of 24	ENSP00000496394.1	Q9H2D6-1
ENSG00000100101	ENST00000455236.4	TSL:5	n.*601C>G		non_coding_transcript_exon	Exon 11 of 13	ENSP00000477208.1	V9GYY5
ENSG00000100101	ENST00000455236.4	TSL:5	n.*601C>G		3_prime_UTR	Exon 11 of 13	ENSP00000477208.1	V9GYY5

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

574

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00439

AC:

1082

AN:

246418

AF XY:

0.00492

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00672

Gnomad OTH exome

AF:

0.00599

GnomAD4 exome

AF:

0.00470

AC:

6871

AN:

1461330

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3402

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33470

American (AMR)

AF:

0.00398

AC:

178

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

311

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00146

AC:

126

AN:

86244

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.0122

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00525

AC:

5839

AN:

1111740

Other (OTH)

AF:

0.00530

AC:

320

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

369

739

1108

1478

1847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<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:

0.00377

AC:

573

AN:

152184

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

240

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41536

American (AMR)

AF:

0.00413

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00610

AC:

415

AN:

68002

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00591

Hom.:

Bravo

AF:

0.00417

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000529

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00453

AC:

547

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0103

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (2)

Autosomal recessive nonsyndromic hearing loss 28 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.039

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.43

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.41

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

REVEL

Benign

0.041

Sift

Benign

0.041

Sift4G

Benign

0.59

Polyphen

0.020

Vest4

0.14

MVP

0.21

MPC

0.12

ClinPred

0.0029

GERP RS

-0.52

Varity_R

0.032

gMVP

0.069

Mutation Taster

=100/0

polymorphism

(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

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

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