rs116448422

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.504C>A(p.Asp168Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,076 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 11 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.388

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 links:

ENSG00000100101 (HGNC:):

ENSG00000100101 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037404597).

BP6

Variant 22-37715810-C-A is Benign according to our data. Variant chr22-37715810-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 227126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (821/152298) while in subpopulation AFR AF= 0.019 (789/41560). AF 95% confidence interval is 0.0179. There are 7 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 linkuse as main transcript	c.504C>A	p.Asp168Glu	missense_variant	6/24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.504C>A	p.Asp168Glu	missense_variant	6/24		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
ENSG00000100101	ENST00000455236.4 linkuse as main transcript	n.*840C>A		non_coding_transcript_exon_variant	12/13	5		ENSP00000477208.1	V9GYY5
ENSG00000100101	ENST00000455236.4 linkuse as main transcript	n.*840C>A		3_prime_UTR_variant	12/13	5		ENSP00000477208.1	V9GYY5

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

821

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00136

AC:

338

AN:

248322

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

134914

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461778

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00539

AC:

821

AN:

152298

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

372

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00609

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00161

AC:

195

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Asp168Glu in Exon 06 of TRIOBP: This variant is not expected to have clinical si gnificance because it has been identified in 2.1% (67/3156) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs116448422). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 31, 2016	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 09, 2024	- -

Autosomal recessive nonsyndromic hearing loss 28

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.36

.;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.98

N;.

REVEL

Benign

0.021

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.17

T;.

Polyphen

0.43

B;B

Vest4

0.15

MutPred

0.13

Gain of glycosylation at P165 (P = 0.1234);Gain of glycosylation at P165 (P = 0.1234);

MVP

0.35

MPC

0.32

ClinPred

0.042

GERP RS

3.0

Varity_R

0.11

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over