NM_001039141.3:c.6472+15_6472+16insC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.6472+15_6472+16insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,585,328 control chromosomes in the GnomAD database, including 47 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 43 hom. )

Consequence

TRIOBP
NM_001039141.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.07

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 -16 ACMG points.

BP6

Variant 22-37765832-G-GC is Benign according to our data. Variant chr22-37765832-G-GC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00447 (676/151322) while in subpopulation AMR AF = 0.00794 (121/15236). AF 95% confidence interval is 0.00679. There are 4 homozygotes in GnomAd4. There are 319 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6472+15_6472+16insC		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1333+15_1333+16insC		intron	N/A	NP_008963.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRIOBP	ENST00000644935.1	MANE Select	c.6472+15_6472+16insC	intron	N/A	ENSP00000496394.1
TRIOBP	ENST00000403663.6	TSL:1	c.1333+15_1333+16insC	intron	N/A	ENSP00000386026.2
TRIOBP	ENST00000344404.10	TSL:2	n.5955+15_5955+16insC	intron	N/A	ENSP00000340312.6

Frequencies

GnomAD3 genomes

AF:

0.00447

AC:

676

AN:

151204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00795

Gnomad ASJ

AF:

0.0151

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000838

Gnomad FIN

AF:

0.000474

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00622

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00440

AC:

890

AN:

202474

AF XY:

0.00428

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000736

Gnomad NFE exome

AF:

0.00597

Gnomad OTH exome

AF:

0.00714

GnomAD4 exome

AF:

0.00611

AC:

8755

AN:

1434006

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4279

AN XY:

711668

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

33100

American (AMR)

AF:

0.00379

AC:

161

AN:

42466

Ashkenazi Jewish (ASJ)

AF:

0.0142

AC:

364

AN:

25708

East Asian (EAS)

AF:

0.00

AC:

AN:

38894

South Asian (SAS)

AF:

0.00201

AC:

168

AN:

83380

European-Finnish (FIN)

AF:

0.000616

AC:

AN:

43824

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

5002

European-Non Finnish (NFE)

AF:

0.00690

AC:

7603

AN:

1102208

Other (OTH)

AF:

0.00602

AC:

358

AN:

59424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

480

961

1441

1922

2402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.00447

AC:

676

AN:

151322

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

319

AN XY:

73964

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

41342

American (AMR)

AF:

0.00794

AC:

121

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.0151

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.000839

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.000474

AC:

AN:

10538

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00622

AC:

420

AN:

67536

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

100

134

167

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:

0.00319

Hom.:

Bravo

AF:

0.00484

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 22, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TRIOBP: BS2

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over