GeneBe

rs376601715

Positions:

Variant summary

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

The NM_001039141.3(TRIOBP):​c.6324+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,609,908 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 0.00019 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.315
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]

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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=-0.82).
BP6
Variant 22-37759273-G-A is Benign according to our data. Variant chr22-37759273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165605.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-37759273-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIOBPNM_001039141.3 linkuse as main transcriptc.6324+9G>A intron_variant ENST00000644935.1 NP_001034230.1
TRIOBPNM_007032.5 linkuse as main transcriptc.1185+9G>A intron_variant NP_008963.3
TRIOBPNM_138632.2 linkuse as main transcriptc.1185+9G>A intron_variant NP_619538.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIOBPENST00000644935.1 linkuse as main transcriptc.6324+9G>A intron_variant NM_001039141.3 ENSP00000496394 A2Q9H2D6-1
TRIOBPENST00000403663.6 linkuse as main transcriptc.1185+9G>A intron_variant 1 ENSP00000386026 P2Q9H2D6-7
TRIOBPENST00000407319.7 linkuse as main transcriptc.1185+9G>A intron_variant 1 ENSP00000383913 Q9H2D6-6
TRIOBPENST00000344404.10 linkuse as main transcriptc.*5807+9G>A intron_variant, NMD_transcript_variant 2 ENSP00000340312

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152112
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000847
AC:
21
AN:
247942
Hom.:
0
AF XY:
0.0000889
AC XY:
12
AN XY:
134950
show subpopulations
Gnomad AFR exome
AF:
0.0000665
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000116
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000251
AC:
366
AN:
1457678
Hom.:
0
Cov.:
30
AF XY:
0.000245
AC XY:
178
AN XY:
725316
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000310
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
152230
Hom.:
0
Cov.:
31
AF XY:
0.000148
AC XY:
11
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000160
Hom.:
0
Bravo
AF:
0.000159
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMay 09, 20136324+9G>A in intron 17 of TRIOBP: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and it has been identified in 0.01% (1/8582) of European American chromosomes and 0. 02% (1/4388) of African American chromosomes by the NHLBI Exome Sequencing Proje ct (http://evs.gs.washington.edu/EVS/) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.53
DANN
Benign
0.22
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

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

Other links and lift over

dbSNP: rs376601715; hg19: chr22-38155280; API