chr22-37723839-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.1283C>G(p.Pro428Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,597,144 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00010 ( 6 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 0.0100

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)
hearing loss, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

TRIOBP links:

ENSG00000100101 (HGNC:):

ENSG00000100101 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008493006).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000239 (36/150396) while in subpopulation EAS AF = 0.00377 (19/5036). AF 95% confidence interval is 0.00247. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.1283C>G	p.Pro428Arg	missense	Exon 7 of 24	NP_001034230.1	Q9H2D6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIOBP	ENST00000644935.1	MANE Select	c.1283C>G	p.Pro428Arg	missense	Exon 7 of 24	ENSP00000496394.1	Q9H2D6-1
ENSG00000100101	ENST00000455236.4	TSL:5	n.*1619C>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000477208.1	V9GYY5
TRIOBP	ENST00000492485.5	TSL:1	n.1217C>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

150280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00376

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00195

GnomAD2 exomes

AF:

0.000136

AC:

AN:

249568

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000100

AC:

145

AN:

1446748

Hom.:

Cov.:

AF XY:

0.0000973

AC XY:

AN XY:

719756

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33328

American (AMR)

AF:

0.0000228

AC:

AN:

43896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.000732

AC:

AN:

39592

South Asian (SAS)

AF:

0.00

AC:

AN:

85750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000545

AC:

AN:

1100794

Other (OTH)

AF:

0.00177

AC:

105

AN:

59454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000239

AC:

AN:

150396

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73440

show subpopulations

African (AFR)

AF:

0.000245

AC:

AN:

40888

American (AMR)

AF:

0.000198

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00377

AC:

AN:

5036

South Asian (SAS)

AF:

0.00

AC:

AN:

4666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67492

Other (OTH)

AF:

0.00192

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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:

0.000432

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.000174

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive nonsyndromic hearing loss 28 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.035

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.40

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.010

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.94

REVEL

Benign

0.052

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0080

Polyphen

0.77

Vest4

0.26

MVP

0.34

MPC

0.45

ClinPred

0.042

GERP RS

1.5

Varity_R

0.056

gMVP

0.032

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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