22-37765828-T-TG

Variant names:

• chr22-37765828-T-TG
• rs3833924
• NM_001039141.3:c.6472+19dupG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001039141.3(TRIOBP):​c.6472+19dupG 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
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6472+19dupG		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1333+19dupG		intron	N/A	NP_008963.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.6472+11_6472+12insG		intron	N/A	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.1333+11_1333+12insG		intron	N/A	ENSP00000386026.2
	TRIOBP	ENST00000344404.10	TSL:2	n.*5955+11_*5955+12insG		intron	N/A	ENSP00000340312.6

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

GnomAD2 exomes AF: 0.597 AC: 105569 AN: 176912 AF XY: 0.592

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 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

African (AFR) AF: 0.814 AC: 25885 AN: 31800

American (AMR) AF: 0.609 AC: 24533 AN: 40278

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 12812 AN: 25110

East Asian (EAS) AF: 0.609 AC: 22962 AN: 37732

South Asian (SAS) AF: 0.569 AC: 46376 AN: 81438

European-Finnish (FIN) AF: 0.588 AC: 24329 AN: 41396

Middle Eastern (MID) AF: 0.586 AC: 2815 AN: 4804

European-Non Finnish (NFE) AF: 0.620 AC: 670092 AN: 1080432

Other (OTH) AF: 0.619 AC: 35965 AN: 58096

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

African (AFR) AF: 0.819 AC: 33756 AN: 41216

American (AMR) AF: 0.646 AC: 9802 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.685 AC: 3491 AN: 5096

South Asian (SAS) AF: 0.584 AC: 2772 AN: 4750

European-Finnish (FIN) AF: 0.624 AC: 6537 AN: 10484

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.630 AC: 42623 AN: 67706

Other (OTH) AF: 0.667 AC: 1393 AN: 2090

Alfa AF: 0.530 Hom.: 2287

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 05, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive nonsyndromic hearing loss 28 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3833924; hg19: chr22-38161835; COSMIC: COSV107427761;