NM_001039141.3:c.5544C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_001039141.3(TRIOBP):c.5544C>T(p.Tyr1848Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,613,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.65

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.028).

BP6

Variant 22-37755157-C-T is Benign according to our data. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37755157-C-T is described in CliVar as Likely_benign. Clinvar id is 178558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.5544C>T	p.Tyr1848Tyr	synonymous_variant	Exon 14 of 24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.405C>T	p.Tyr135Tyr	synonymous_variant	Exon 4 of 14		NP_008963.3	Q9H2D6-7
TRIOBP	NM_138632.2 link	c.405C>T	p.Tyr135Tyr	synonymous_variant	Exon 4 of 8		NP_619538.2	Q9H2D6-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1 link	c.5544C>T	p.Tyr1848Tyr	synonymous_variant	Exon 14 of 24		NM_001039141.3	ENSP00000496394.1		Q9H2D6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000722

AC:

AN:

249218

AF XY:

0.0000593

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461074

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726766

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33450

American (AMR)

AF:

0.000202

AC:

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.000105

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1111654

Other (OTH)

AF:

0.0000497

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000135

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 10, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Tyr1848Tyr in exon 14 of TRIOBP: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 2/14690 South Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs373713130). -

not provided

Benign:1

Oct 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.64

(source)

DANN

Benign

0.89

PhyloP100

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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