22-37734465-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039141.3(TRIOBP):c.4129T>C(p.Trp1377Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 1,612,998 control chromosomes in the GnomAD database, including 741,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71501 hom., cov: 31)

Exomes 𝑓: 0.96 ( 669656 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.415

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:

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=7.24621E-7).

BP6

Variant 22-37734465-T-C is Benign according to our data. Variant chr22-37734465-T-C is described in ClinVar as [Benign]. Clinvar id is 43855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37734465-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.4129T>C	p.Trp1377Arg	missense_variant	Exon 9 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.4129T>C	p.Trp1377Arg	missense_variant	Exon 9 of 24		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000344404.10 link	n.*3612T>C		non_coding_transcript_exon_variant	Exon 7 of 22	2		ENSP00000340312.6	H7BXW4
TRIOBP	ENST00000344404.10 link	n.*3612T>C		3_prime_UTR_variant	Exon 7 of 22	2		ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.969

AC:

147393

AN:

152124

Hom.:

71440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.991

Gnomad AMI

AF:

0.979

Gnomad AMR

AF:

0.968

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.977

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.953

Gnomad OTH

AF:

0.965

GnomAD3 exomes

AF:

0.966

AC:

238692

AN:

247150

Hom.:

115320

AF XY:

0.966

AC XY:

130091

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.991

Gnomad AMR exome

AF:

0.977

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.975

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.957

GnomAD4 exome

AF:

0.957

AC:

1398449

AN:

1460756

Hom.:

669656

Cov.:

AF XY:

0.958

AC XY:

696107

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.993

Gnomad4 AMR exome

AF:

0.976

Gnomad4 ASJ exome

AF:

0.912

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.971

Gnomad4 NFE exome

AF:

0.951

Gnomad4 OTH exome

AF:

0.959

GnomAD4 genome

AF:

0.969

AC:

147513

AN:

152242

Hom.:

71501

Cov.:

AF XY:

0.970

AC XY:

72233

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.991

Gnomad4 AMR

AF:

0.968

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.977

Gnomad4 NFE

AF:

0.953

Gnomad4 OTH

AF:

0.965

Alfa

AF:

0.952

Hom.:

101254

Bravo

AF:

0.969

TwinsUK

AF:

0.946

AC:

3506

ALSPAC

AF:

0.954

AC:

3676

ESP6500AA

AF:

0.989

AC:

3817

ESP6500EA

AF:

0.953

AC:

7866

ExAC

AF:

0.965

AC:

116460

Asia WGS

AF:

0.994

AC:

3458

AN:

3478

EpiCase

AF:

0.950

EpiControl

AF:

0.945

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Trp1377Arg in Exon 09 of TRIOBP: This variant is not expected to have clinical s ignificance because it has been identified in 4.7% (311/6656) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs8140958). -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 28

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.63

DANN

Benign

0.42

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.066

.;T

MetaRNN

Benign

7.2e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

3.0

N;.

REVEL

Benign

0.038

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;B

Vest4

0.015

MutPred

0.10

Gain of methylation at W1377 (P = 0.0191);Gain of methylation at W1377 (P = 0.0191);

MPC

0.21

ClinPred

0.0010

GERP RS

0.85

Varity_R

0.043

gMVP

0.042

Splicing

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