rs144634857

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.391G>A(p.Gly131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,613,934 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 38 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.333

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 links:

ENSG00000100101 (HGNC:):

ENSG00000100101 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030972362).

BP6

Variant 22-37713346-G-A is Benign according to our data. Variant chr22-37713346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37713346-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00456 (694/152242) while in subpopulation AMR AF= 0.00707 (108/15270). AF 95% confidence interval is 0.00599. There are 5 homozygotes in gnomad4. There are 337 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 5 of 24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000644935.1 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 5 of 24		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
ENSG00000100101	ENST00000455236.4 link	n.*727G>A		non_coding_transcript_exon_variant	Exon 11 of 13	5		ENSP00000477208.1	V9GYY5
ENSG00000100101	ENST00000455236.4 link	n.*727G>A		3_prime_UTR_variant	Exon 11 of 13	5		ENSP00000477208.1	V9GYY5

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

693

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00553

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00502

AC:

1252

AN:

249182

Hom.:

AF XY:

0.00517

AC XY:

699

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.0294

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.000233

Gnomad NFE exome

AF:

0.00632

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00516

AC:

7543

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

3821

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.0277

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.00526

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152242

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

337

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00707

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00553

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.00499

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000939

AC:

ESP6500EA

AF:

0.00693

AC:

ExAC

AF:

0.00465

AC:

563

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00800

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 31, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRIOBP: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:3

Mar 31, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gly131Ser in Exon 05 of TRIOBP: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (47/6930) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs144634857). -

Mar 01, 2016

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.3

DANN

Benign

0.88

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.32

.;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.052

Sift

Benign

0.42

T;.

Sift4G

Benign

0.74

T;.

Polyphen

0.066

B;B

Vest4

0.14

MVP

0.14

MPC

0.12

ClinPred

0.00037

GERP RS

-4.6

Varity_R

0.014

gMVP

0.064

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over