Genetic Variant TRIOBP:c.6472+14G>A (chr22-37765831-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039141.3(TRIOBP):c.6472+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,586,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

TRIOBP
NM_001039141.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.772

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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+14G>A		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1333+14G>A		intron	N/A	NP_008963.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TRIOBP	ENST00000644935.1	MANE Select	c.6472+14G>A	intron	N/A	ENSP00000496394.1
TRIOBP	ENST00000403663.6	TSL:1	c.1333+14G>A	intron	N/A	ENSP00000386026.2
TRIOBP	ENST00000344404.10	TSL:2	n.*5955+14G>A	intron	N/A	ENSP00000340312.6

Frequencies

GnomAD3 genomes

AF:

0.0000595

AC:

AN:

151328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000493

AC:

AN:

202864

AF XY:

0.0000357

show subpopulations

Gnomad AFR exome

AF:

0.000174

Gnomad AMR exome

AF:

0.0000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000253

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1434600

Hom.:

Cov.:

AF XY:

0.0000464

AC XY:

AN XY:

711960

show subpopulations

African (AFR)

AF:

0.0000907

AC:

AN:

33060

American (AMR)

AF:

0.0000706

AC:

AN:

42482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25740

East Asian (EAS)

AF:

0.000360

AC:

AN:

38872

South Asian (SAS)

AF:

0.000156

AC:

AN:

83476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5014

European-Non Finnish (NFE)

AF:

0.0000263

AC:

AN:

1102632

Other (OTH)

AF:

0.0000168

AC:

AN:

59444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000594

AC:

AN:

151444

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.0000729

AC:

AN:

41160

American (AMR)

AF:

0.0000658

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5130

South Asian (SAS)

AF:

0.000208

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

67774

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.9

(source)

DANN

Benign

0.80

PhyloP100

-0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

Other links and lift over