rs547759535

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001039141.3(TRIOBP):c.4329A>G(p.Leu1443=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,600,124 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 3 hom. )

Consequence

TRIOBP
NM_001039141.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.495

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-37734665-A-G is Benign according to our data. Variant chr22-37734665-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 165593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37734665-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.495 with no splicing effect.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3 linkuse as main transcript	c.4329A>G	p.Leu1443=	synonymous_variant	9/24	ENST00000644935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.4329A>G	p.Leu1443=	synonymous_variant	9/24		NM_001039141.3	A2	Q9H2D6-1
TRIOBP	ENST00000344404.10 linkuse as main transcript	c.*3812A>G		3_prime_UTR_variant, NMD_transcript_variant	7/22	2

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000544

AC:

118

AN:

216758

Hom.:

AF XY:

0.000544

AC XY:

AN XY:

119426

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000351

Gnomad ASJ exome

AF:

0.00884

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000701

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.000918

GnomAD4 exome

AF:

0.000256

AC:

371

AN:

1447920

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

193

AN XY:

719194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000332

Gnomad4 ASJ exome

AF:

0.00840

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000945

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000633

Gnomad4 OTH exome

AF:

0.000969

GnomAD4 genome

AF:

0.000348

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000932

Hom.:

Bravo

AF:

0.000468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 18, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 31, 2013

Leu1443Leu in exon 9 of TRIOBP: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.4

Dann

Benign

0.61

Splicing

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