rs34655947

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001039141.3(TRIOBP):c.5488-7delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,276 control chromosomes in the GnomAD database, including 2,803 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 298 hom., cov: 31)

Exomes 𝑓: 0.057 ( 2505 hom. )

Consequence

TRIOBP
NM_001039141.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.100

Publications

2 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 -16 ACMG points.

BP6

Variant 22-37755093-TG-T is Benign according to our data. Variant chr22-37755093-TG-T is described in ClinVar as Benign. ClinVar VariationId is 43861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.5488-7delG	splice_region_variant, intron_variant	Intron 13 of 23	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.349-7delG	splice_region_variant, intron_variant	Intron 3 of 13		NP_008963.3	Q9H2D6-7
TRIOBP	NM_138632.2 link	c.349-7delG	splice_region_variant, 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.5488-7delG		splice_region_variant, intron_variant	Intron 13 of 23		NM_001039141.3	ENSP00000496394.1		Q9H2D6-1

Frequencies

GnomAD3 genomes

AF:

0.0599

AC:

9119

AN:

152144

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.0426

Gnomad SAS

AF:

0.0391

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0606

Gnomad OTH

AF:

0.0469

GnomAD2 exomes

AF:

0.0580

AC:

14445

AN:

249054

AF XY:

0.0541

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0386

Gnomad EAS exome

AF:

0.0452

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0556

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0567

AC:

82792

AN:

1461014

Hom.:

2505

Cov.:

AF XY:

0.0553

AC XY:

40195

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.0560

AC:

1874

AN:

33444

American (AMR)

AF:

0.104

AC:

4626

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.0423

AC:

1106

AN:

26124

East Asian (EAS)

AF:

0.0322

AC:

1278

AN:

39666

South Asian (SAS)

AF:

0.0337

AC:

2901

AN:

86148

European-Finnish (FIN)

AF:

0.0539

AC:

2875

AN:

53292

Middle Eastern (MID)

AF:

0.0212

AC:

122

AN:

5766

European-Non Finnish (NFE)

AF:

0.0581

AC:

64580

AN:

1111610

Other (OTH)

AF:

0.0568

AC:

3430

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

4650

9301

13951

18602

23252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2392

4784

7176

9568

11960

<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:

0.0599

AC:

9124

AN:

152262

Hom.:

298

Cov.:

AF XY:

0.0600

AC XY:

4469

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0541

AC:

2249

AN:

41558

American (AMR)

AF:

0.0917

AC:

1403

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

140

AN:

3468

East Asian (EAS)

AF:

0.0427

AC:

221

AN:

5172

South Asian (SAS)

AF:

0.0394

AC:

190

AN:

4824

European-Finnish (FIN)

AF:

0.0574

AC:

609

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0606

AC:

4122

AN:

68014

Other (OTH)

AF:

0.0469

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

422

844

1266

1688

2110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0599

Asia WGS

AF:

0.0440

AC:

156

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

5488-7delG in intron 13 of TRIOBP: This variant is not expected to have clinical significance because it has been identified in 4.5% (97/2178) of chromosomes fr om a broad population (1000Genomes; dbSNP rs34655947) -

not provided

Benign:2

Jun 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.10

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over