chr22-37754993-A-G

Variant names:

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.5487+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,678 control chromosomes in the GnomAD database, including 1,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 170 hom., cov: 32)

Exomes 𝑓: 0.028 ( 849 hom. )

Consequence

TRIOBP
NM_001039141.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.40

Publications

1 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), PanelApp Australia
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 (BayesDel_noAF=-0.88).

BP6

Variant 22-37754993-A-G is Benign according to our data. Variant chr22-37754993-A-G is described in ClinVar as Benign. ClinVar VariationId is 43860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.5487+9A>G	intron_variant	Intron 13 of 23	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.348+9A>G	intron_variant	Intron 3 of 13		NP_008963.3	Q9H2D6-7
TRIOBP	NM_138632.2 link	c.348+9A>G	intron_variant	Intron 3 of 7		NP_619538.2	Q9H2D6-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1 link	c.5487+9A>G		intron_variant	Intron 13 of 23		NM_001039141.3	ENSP00000496394.1		Q9H2D6-1

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6185

AN:

152182

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0767

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0338

AC:

8454

AN:

250168

AF XY:

0.0353

show subpopulations

Gnomad AFR exome

AF:

0.0726

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0608

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0319

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0328

GnomAD4 exome

AF:

0.0280

AC:

40974

AN:

1461378

Hom.:

849

Cov.:

AF XY:

0.0295

AC XY:

21429

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.0770

AC:

2576

AN:

33470

American (AMR)

AF:

0.0185

AC:

828

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

1490

AN:

26118

East Asian (EAS)

AF:

0.000151

AC:

AN:

39690

South Asian (SAS)

AF:

0.0728

AC:

6273

AN:

86178

European-Finnish (FIN)

AF:

0.0310

AC:

1656

AN:

53364

Middle Eastern (MID)

AF:

0.0717

AC:

413

AN:

5764

European-Non Finnish (NFE)

AF:

0.0232

AC:

25821

AN:

1111738

Other (OTH)

AF:

0.0317

AC:

1911

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2386

4772

7157

9543

11929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1036

2072

3108

4144

5180

<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:

0.0406

AC:

6188

AN:

152300

Hom.:

170

Cov.:

AF XY:

0.0413

AC XY:

3078

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0744

AC:

3093

AN:

41550

American (AMR)

AF:

0.0231

AC:

354

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

193

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0769

AC:

371

AN:

4822

European-Finnish (FIN)

AF:

0.0347

AC:

368

AN:

10618

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0238

AC:

1617

AN:

68036

Other (OTH)

AF:

0.0407

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

303

605

908

1210

1513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0347

Hom.:

Bravo

AF:

0.0400

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

5487+9A>G in Intron 13 of TRIOBP: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 7.2% (269/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs56016429). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 24, 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:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

(source)

DANN

Benign

0.68

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over