rs774610362

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001039141.3(TRIOBP):​c.5266C>A​(p.Arg1756Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

Publications

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP7
Synonymous conserved (PhyloP=2.46 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIOBPNM_001039141.3 linkc.5266C>A p.Arg1756Arg synonymous_variant Exon 11 of 24 ENST00000644935.1 NP_001034230.1 Q9H2D6-1
LOC124905115XM_047441691.1 linkc.19-217G>T intron_variant Intron 1 of 2 XP_047297647.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIOBPENST00000644935.1 linkc.5266C>A p.Arg1756Arg synonymous_variant Exon 11 of 24 NM_001039141.3 ENSP00000496394.1 Q9H2D6-1
TRIOBPENST00000344404.10 linkn.*4749C>A non_coding_transcript_exon_variant Exon 9 of 22 2 ENSP00000340312.6 H7BXW4
TRIOBPENST00000344404.10 linkn.*4749C>A 3_prime_UTR_variant Exon 9 of 22 2 ENSP00000340312.6 H7BXW4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408384
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
695350
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32416
American (AMR)
AF:
0.00
AC:
0
AN:
36208
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25242
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37010
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79842
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49708
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5706
European-Non Finnish (NFE)
AF:
9.23e-7
AC:
1
AN:
1083862
Other (OTH)
AF:
0.00
AC:
0
AN:
58390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
CADD
Benign
12
DANN
Benign
0.82
PhyloP100
2.5

Splicing

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

Publications

Other links and lift over

dbSNP: rs774610362; hg19: chr22-38136983; API