rs200793989

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_001039141.3(TRIOBP):c.6771G>A(p.Gln2257Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000883 in 1,612,026 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.495

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)
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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 22-37769297-G-A is Benign according to our data. Variant chr22-37769297-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 228042.

BP7

Synonymous conserved (PhyloP=0.495 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000921 (1344/1459632) while in subpopulation NFE AF = 0.00116 (1288/1111450). AF 95% confidence interval is 0.00111. There are 0 homozygotes in GnomAdExome4. There are 658 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6771G>A	p.Gln2257Gln	synonymous	Exon 21 of 24	NP_001034230.1	Q9H2D6-1
	TRIOBP	NM_007032.5		c.1632G>A	p.Gln544Gln	synonymous	Exon 11 of 14	NP_008963.3	Q9H2D6-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIOBP	ENST00000644935.1	MANE Select	c.6771G>A	p.Gln2257Gln	synonymous	Exon 21 of 24	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000403663.6	TSL:1	c.1632G>A	p.Gln544Gln	synonymous	Exon 11 of 14	ENSP00000386026.2	Q9H2D6-7
TRIOBP	ENST00000344404.10	TSL:2	n.*6254G>A		non_coding_transcript_exon	Exon 19 of 22	ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.000525

AC:

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000521

AC:

127

AN:

243814

AF XY:

0.000503

show subpopulations

Gnomad AFR exome

AF:

0.000269

Gnomad AMR exome

AF:

0.000496

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.000507

GnomAD4 exome

AF:

0.000921

AC:

1344

AN:

1459632

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

658

AN XY:

726074

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33440

American (AMR)

AF:

0.000471

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00116

AC:

1288

AN:

1111450

Other (OTH)

AF:

0.000497

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

171

257

342

428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<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:

0.000518

AC:

AN:

152394

Hom.:

Cov.:

AF XY:

0.000496

AC XY:

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.000264

AC:

AN:

41598

American (AMR)

AF:

0.000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.000803

Hom.:

Bravo

AF:

0.000533

EpiCase

AF:

0.00104

EpiControl

AF:

0.000952

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

TRIOBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.3

(source)

DANN

Benign

0.89

PhyloP100

0.49

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

Computational scores

Splicing

Publications

Other links and lift over