Variant chr22-37755093-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001039141.3(TRIOBP):c.5488-7del variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.100

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	MANE
TRIOBP	NM_001039141.3 linkuse as main transcript	c.5488-7del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000644935.1
TRIOBP	NM_007032.5 linkuse as main transcript	c.349-7del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TRIOBP	NM_138632.2 linkuse as main transcript	c.349-7del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.5488-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001039141.3	A2	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

GnomAD3 exomes

AF:

0.0580

AC:

14445

AN:

249054

Hom.:

492

AF XY:

0.0541

AC XY:

7291

AN XY:

134748

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 SAS exome

AF:

0.0328

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

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.0322

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0539

Gnomad4 NFE exome

AF:

0.0581

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0599

AC:

9124

AN:

152262

Hom.:

298

Cov.:

AF XY:

0.0600

AC XY:

4469

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0541

Gnomad4 AMR

AF:

0.0917

Gnomad4 ASJ

AF:

0.0404

Gnomad4 EAS

AF:

0.0427

Gnomad4 SAS

AF:

0.0394

Gnomad4 FIN

AF:

0.0574

Gnomad4 NFE

AF:

0.0606

Gnomad4 OTH

AF:

0.0469

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 20, 2012	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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