rs34066624

Positions:

chr22-37733381-G-A

Variant summary

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

The NM_001039141.3(TRIOBP):c.4031G>A(p.Arg1344Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00365 in 1,551,186 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 16 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 6.34

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=0.008185834).

BP6

Variant 22-37733381-G-A is Benign according to our data. Variant chr22-37733381-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37733381-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00228 (348/152334) while in subpopulation NFE AF= 0.0036 (245/68024). AF 95% confidence interval is 0.00323. There are 1 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 linkuse as main transcript	c.4031G>A	p.Arg1344Gln	missense_variant	8/24	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.4031G>A	p.Arg1344Gln	missense_variant	8/24		NM_001039141.3	ENSP00000496394	A2	Q9H2D6-1
TRIOBP	ENST00000344404.10 linkuse as main transcript	c.*3514G>A		3_prime_UTR_variant, NMD_transcript_variant	6/22	2		ENSP00000340312

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

348

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00360

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00251

AC:

389

AN:

155072

Hom.:

AF XY:

0.00241

AC XY:

199

AN XY:

82546

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.0000915

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.000935

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00380

AC:

5316

AN:

1398852

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2541

AN XY:

689990

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00814

Gnomad4 EAS exome

AF:

0.0000559

Gnomad4 SAS exome

AF:

0.000669

Gnomad4 FIN exome

AF:

0.000808

Gnomad4 NFE exome

AF:

0.00440

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00228

AC:

348

AN:

152334

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00360

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000516

AC:

ESP6500EA

AF:

0.00377

AC:

ExAC

AF:

0.00122

AC:

110

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 24, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	TRIOBP: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 08, 2017	- -

Autosomal recessive nonsyndromic hearing loss 28

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	May 03, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

Arg1344Gln in Exon 08 of TRIOBP: This variant is not expected to have clinical s ignificance because it has been identified in 0.5% (30/6466) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs34066624). -

TRIOBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Deafness

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.042

T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.55

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.10

T;.

Polyphen

1.0

D;D

Vest4

0.24

MVP

0.57

MPC

0.39

ClinPred

0.037

GERP RS

5.8

Varity_R

0.22

gMVP

0.19

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