rs34316404

Variant names:

• chr22-37701198-T-TAA
• rs34316404
• NM_001039141.3:c.-60-107_-60-106dupAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001039141.3(TRIOBP):​c.-60-107_-60-106dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 625,720 control chromosomes in the GnomAD database, including 25,257 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5040 hom., cov: 23)
  • Exomes 𝑓: 0.28 (20217 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470
• Publications: 1 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

ENSG00000100101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 22-37701198-T-TAA is Benign according to our data. Variant chr22-37701198-T-TAA is described in ClinVar as Benign. ClinVar VariationId is 1234293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.375 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.-60-107_-60-106dupAA		intron	N/A	NP_001034230.1	Q9H2D6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.-60-108_-60-107insAA		intron	N/A	ENSP00000496394.1	Q9H2D6-1
	ENSG00000100101	ENST00000455236.4	TSL:5	n.*277-108_*277-107insAA		intron	N/A	ENSP00000477208.1	V9GYY5
	TRIOBP	ENST00000492485.5	TSL:1	n.77-108_77-107insAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38315 AN: 151836 Hom.: 5037 Cov.: 23

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.284 AC: 134642 AN: 473766 Hom.: 20217 AF XY: 0.290 AC XY: 73118 AN XY: 252454

African (AFR) AF: 0.170 AC: 2359 AN: 13874

American (AMR) AF: 0.213 AC: 6029 AN: 28314

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 5354 AN: 15832

East Asian (EAS) AF: 0.208 AC: 6177 AN: 29626

South Asian (SAS) AF: 0.380 AC: 20329 AN: 53558

European-Finnish (FIN) AF: 0.314 AC: 9439 AN: 30102

Middle Eastern (MID) AF: 0.345 AC: 732 AN: 2122

European-Non Finnish (NFE) AF: 0.281 AC: 76809 AN: 273756

Other (OTH) AF: 0.279 AC: 7414 AN: 26582

GnomAD4 genome AF: 0.252 AC: 38351 AN: 151954 Hom.: 5040 Cov.: 23 AF XY: 0.256 AC XY: 19008 AN XY: 74248

African (AFR) AF: 0.177 AC: 7356 AN: 41452

American (AMR) AF: 0.238 AC: 3631 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3470

East Asian (EAS) AF: 0.174 AC: 896 AN: 5162

South Asian (SAS) AF: 0.389 AC: 1876 AN: 4818

European-Finnish (FIN) AF: 0.334 AC: 3510 AN: 10524

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18980 AN: 67936

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.268 Hom.: 646

Bravo AF: 0.238

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.047
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: rs34316404; hg19: chr22-38097205;