ENST00000407319.7:c.1269G>A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000407319.7(TRIOBP):c.1269G>A(p.Pro423Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000467 in 1,605,618 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

TRIOBP
ENST00000407319.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.293

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-37759500-G-A is Benign according to our data. Variant chr22-37759500-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 504695.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.6324+236G>A		intron_variant	Intron 17 of 23	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_138632.2 link	c.1269G>A	p.Pro423Pro	synonymous_variant	Exon 8 of 8		NP_619538.2	Q9H2D6-6
TRIOBP	NM_007032.5 link	c.1185+236G>A		intron_variant	Intron 7 of 13		NP_008963.3	Q9H2D6-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000407319.7 link	c.1269G>A	p.Pro423Pro	synonymous_variant	Exon 8 of 8	1		ENSP00000383913.2	Q9H2D6-6
TRIOBP	ENST00000644935.1 link	c.6324+236G>A		intron_variant	Intron 17 of 23		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000403663.6 link	c.1185+236G>A		intron_variant	Intron 7 of 13	1		ENSP00000386026.2	Q9H2D6-7
TRIOBP	ENST00000344404.10 link	n.*5807+236G>A		intron_variant	Intron 15 of 21	2		ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000366

AC:

AN:

245996

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000482

AC:

AN:

1453420

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

723512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000551

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000615

Hom.:

Bravo

AF:

0.0000416

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Pro423Pro in exon 8 of TRIOBP (NM_138632.2): This variant is not expected to h ave clinical significance because it does not alter an amino acid residue, is no t located within the splice consensus sequence, and has been identified in 4/662 02 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs140572991). In addition, the variant occurs in the co ding region of one transcript isoform of the gene and lies in an intronic region in other transcript isoforms of TRIOBP (NM_001039141.2, NM_007032.5). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.70

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