rs7284476

Variant names:

• chr22-37733325-G-A
• rs7284476
• NM_001039141.3:c.3975G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37733325-G-A
• chr22-37733325-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001039141.3(TRIOBP):​c.3975G>A​(p.Gln1325Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,550,746 control chromosomes in the GnomAD database, including 144,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10845 hom., cov: 33)
  • Exomes 𝑓: 0.43 (133426 hom.)
• Consequence: TRIOBP NM_001039141.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.43
• Publications: 30 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 22-37733325-G-A is Benign according to our data. Variant chr22-37733325-G-A is described in ClinVar as Benign. ClinVar VariationId is 43851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 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.3975G>A	p.Gln1325Gln	synonymous	Exon 8 of 24	NP_001034230.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.3975G>A	p.Gln1325Gln	synonymous	Exon 8 of 24	ENSP00000496394.1
	TRIOBP	ENST00000344404.10	TSL:2	n.*3458G>A		non_coding_transcript_exon	Exon 6 of 22	ENSP00000340312.6
	TRIOBP	ENST00000344404.10	TSL:2	n.*3458G>A		3_prime_UTR	Exon 6 of 22	ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54479 AN: 151978 Hom.: 10841 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.395 AC: 61023 AN: 154642 AF XY: 0.393

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.601

Gnomad FIN exome AF: 0.351

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.432 AC: 604605 AN: 1398648 Hom.: 133426 Cov.: 48 AF XY: 0.429 AC XY: 296215 AN XY: 689918

African (AFR) AF: 0.187 AC: 5923 AN: 31612

American (AMR) AF: 0.349 AC: 12504 AN: 35792

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8541 AN: 25184

East Asian (EAS) AF: 0.555 AC: 19862 AN: 35788

South Asian (SAS) AF: 0.351 AC: 27842 AN: 79284

European-Finnish (FIN) AF: 0.362 AC: 17478 AN: 48232

Middle Eastern (MID) AF: 0.297 AC: 1690 AN: 5694

European-Non Finnish (NFE) AF: 0.451 AC: 486885 AN: 1079050

Other (OTH) AF: 0.412 AC: 23880 AN: 58012

GnomAD4 genome AF: 0.358 AC: 54495 AN: 152098 Hom.: 10845 Cov.: 33 AF XY: 0.355 AC XY: 26396 AN XY: 74344

African (AFR) AF: 0.194 AC: 8066 AN: 41514

American (AMR) AF: 0.347 AC: 5300 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3072 AN: 5170

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4834

European-Finnish (FIN) AF: 0.364 AC: 3857 AN: 10582

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30177 AN: 67948

Other (OTH) AF: 0.349 AC: 734 AN: 2104

Alfa AF: 0.408 Hom.: 31327

Bravo AF: 0.350

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gln1325Gln in Exon 08 of TRIOBP: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 43.7% (2800/6406) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7284476).

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		3.4
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: rs7284476; hg19: chr22-38129332; COSMIC: COSV60378278;