rs34655947

Positions:

• chr22-37755093-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001039141.3(TRIOBP):​c.5488-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,276 control chromosomes in the GnomAD database, including 2,803 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (298 hom., cov: 31)
  • Exomes 𝑓: 0.057 (2505 hom.)
• Consequence: TRIOBP NM_001039141.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.100

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-37755093-TG-T is Benign according to our data. Variant chr22-37755093-TG-T is described in ClinVar as [Benign]. Clinvar id is 43861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.5488-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.349-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TRIOBP	NM_138632.2	c.349-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.5488-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001039141.3	A2

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9119 AN: 152144 Hom.: 298 Cov.: 31

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0469

GnomAD3 exomes AF: 0.0580 AC: 14445 AN: 249054 Hom.: 492 AF XY: 0.0541 AC XY: 7291 AN XY: 134748

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.0452

Gnomad SAS exome AF: 0.0328

Gnomad FIN exome AF: 0.0505

Gnomad NFE exome AF: 0.0556

Gnomad OTH exome AF: 0.0533

GnomAD4 exome AF: 0.0567 AC: 82792 AN: 1461014 Hom.: 2505 Cov.: 32 AF XY: 0.0553 AC XY: 40195 AN XY: 726764

Gnomad4 AFR exome AF: 0.0560

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0423

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.0337

Gnomad4 FIN exome AF: 0.0539

Gnomad4 NFE exome AF: 0.0581

Gnomad4 OTH exome AF: 0.0568

GnomAD4 genome AF: 0.0599 AC: 9124 AN: 152262 Hom.: 298 Cov.: 31 AF XY: 0.0600 AC XY: 4469 AN XY: 74446

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.0427

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0606

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0347 Hom.: 33

Bravo AF: 0.0599

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 20, 2012	5488-7delG in intron 13 of TRIOBP: This variant is not expected to have clinical significance because it has been identified in 4.5% (97/2178) of chromosomes fr om a broad population (1000Genomes; dbSNP rs34655947) -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34655947; hg19: chr22-38151100;