22-37765831-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001039141.3(TRIOBP):​c.6472+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,586,044 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 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.772
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 Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 22-37765831-G-C is Benign according to our data. Variant chr22-37765831-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1632594.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00035 (53/151444) while in subpopulation AFR AF= 0.00114 (47/41160). AF 95% confidence interval is 0.000882. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIOBPNM_001039141.3 linkc.6472+14G>C intron_variant Intron 18 of 23 ENST00000644935.1 NP_001034230.1 Q9H2D6-1
TRIOBPNM_007032.5 linkc.1333+14G>C intron_variant Intron 8 of 13 NP_008963.3 Q9H2D6-7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIOBPENST00000644935.1 linkc.6472+14G>C intron_variant Intron 18 of 23 NM_001039141.3 ENSP00000496394.1 Q9H2D6-1
TRIOBPENST00000403663.6 linkc.1333+14G>C intron_variant Intron 8 of 13 1 ENSP00000386026.2 Q9H2D6-7
TRIOBPENST00000344404.10 linkn.*5955+14G>C intron_variant Intron 16 of 21 2 ENSP00000340312.6 H7BXW4

Frequencies

GnomAD3 genomes
AF:
0.000344
AC:
52
AN:
151328
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
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:
0.0000590
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
22
AN:
202864
Hom.:
0
AF XY:
0.0000802
AC XY:
9
AN XY:
112200
show subpopulations
Gnomad AFR exome
AF:
0.000872
Gnomad AMR exome
AF:
0.000159
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000732
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000554
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000118
AC:
169
AN:
1434600
Hom.:
0
Cov.:
34
AF XY:
0.000115
AC XY:
82
AN XY:
711960
show subpopulations
Gnomad4 AFR exome
AF:
0.000726
Gnomad4 AMR exome
AF:
0.000118
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000129
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.000168
GnomAD4 genome
AF:
0.000350
AC:
53
AN:
151444
Hom.:
0
Cov.:
32
AF XY:
0.000338
AC XY:
25
AN XY:
74038
show subpopulations
Gnomad4 AFR
AF:
0.00114
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000590
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000367
Hom.:
0
Bravo
AF:
0.000431

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.6
DANN
Benign
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs45503898; hg19: chr22-38161838; API