NM_001039141.3:c.5886A>G

Variant names:

• chr22-37757811-A-G
• rs372220018
• NM_001039141.3:c.5886A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001039141.3(TRIOBP):​c.5886A>G​(p.Pro1962Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,548,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: TRIOBP NM_001039141.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.361
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP6: Variant 22-37757811-A-G is Benign according to our data. Variant chr22-37757811-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.361 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00163 (248/152262) while in subpopulation AFR AF = 0.00558 (232/41570). AF 95% confidence interval is 0.00499. There are 0 homozygotes in GnomAd4. There are 111 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.5886A>G	p.Pro1962Pro	synonymous	Exon 16 of 24	NP_001034230.1
	TRIOBP	NM_007032.5		c.747A>G	p.Pro249Pro	synonymous	Exon 6 of 14	NP_008963.3
	TRIOBP	NM_138632.2		c.747A>G	p.Pro249Pro	synonymous	Exon 6 of 8	NP_619538.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.5886A>G	p.Pro1962Pro	synonymous	Exon 16 of 24	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.747A>G	p.Pro249Pro	synonymous	Exon 6 of 14	ENSP00000386026.2
	TRIOBP	ENST00000407319.7	TSL:1	c.747A>G	p.Pro249Pro	synonymous	Exon 6 of 8	ENSP00000383913.2

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

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: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000281 AC: 42 AN: 149486 AF XY: 0.000238

Gnomad AFR exome AF: 0.00480

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000233

GnomAD4 exome AF: 0.000150 AC: 209 AN: 1395838 Hom.: 1 Cov.: 32 AF XY: 0.000116 AC XY: 80 AN XY: 688108

African (AFR) AF: 0.00542 AC: 171 AN: 31572

American (AMR) AF: 0.000336 AC: 12 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25044

East Asian (EAS) AF: 0.00 AC: 0 AN: 35782

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47650

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5658

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1077348

Other (OTH) AF: 0.000363 AC: 21 AN: 57876

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74448

African (AFR) AF: 0.00558 AC: 232 AN: 41570

American (AMR) AF: 0.000850 AC: 13 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.00175

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRIOBP: BP4, BP7

Dec 16, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro1962Pro in Exon 16 of TRIOBP: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.2% (6/3446) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.52
PhyloP100		-0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs372220018; hg19: chr22-38153818;