22-37765828-TGG-TGGG

Variant summary

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

The NM_001039141.3(TRIOBP):c.6472+19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,552,260 control chromosomes in the GnomAD database, including 299,351 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35595 hom., cov: 0)
  • Exomes 𝑓: 0.62 (263756 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.29

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 22-37765828-T-TG is Benign according to our data. Variant chr22-37765828-T-TG is described in ClinVar as [Benign]. Clinvar id is 257225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.6472+19dup		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.1333+19dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+19dup		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000403663.6	c.1333+19dup		intron_variant		1		P2
TRIOBP	ENST00000344404.10	c.*5955+19dup		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.681 AC: 102809 AN: 151056 Hom.: 35570 Cov.: 0

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.665

GnomAD3 exomes AF: 0.597 AC: 105569 AN: 176912 Hom.: 30378 AF XY: 0.592 AC XY: 57944 AN XY: 97906

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.497

Gnomad EAS exome AF: 0.661

Gnomad SAS exome AF: 0.554

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.618 AC: 865769 AN: 1401086 Hom.: 263756 Cov.: 34 AF XY: 0.615 AC XY: 426816 AN XY: 694288

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.681 AC: 102894 AN: 151174 Hom.: 35595 Cov.: 0 AF XY: 0.677 AC XY: 49991 AN XY: 73788

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.667

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Eurofins Ntd Llc (ga)	May 05, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 13, 2019	- -

Autosomal recessive nonsyndromic hearing loss 28 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3833924; hg19: chr22-38161835;