22-37765832-G-GT

Variant names:

• chr22-37765832-G-GT
• rs149021782
• NM_001039141.3:c.6472+15_6472+16insT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001039141.3(TRIOBP):​c.6472+15_6472+16insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,585,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 22-37765832-G-GT is Benign according to our data. Variant chr22-37765832-G-GT is described in ClinVar as Likely_benign. ClinVar VariationId is 2955208.Status of the report is criteria_provided_single_submitter, 1 stars.

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+15_6472+16insT		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1333+15_1333+16insT		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+15_6472+16insT		intron	N/A	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.1333+15_1333+16insT		intron	N/A	ENSP00000386026.2
	TRIOBP	ENST00000344404.10	TSL:2	n.*5955+15_*5955+16insT		intron	N/A	ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.0000642 AC: 13 AN: 202474 AF XY: 0.0000536

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000629

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000555

Gnomad OTH exome AF: 0.000193

GnomAD4 exome AF: 0.0000879 AC: 126 AN: 1434018 Hom.: 0 Cov.: 35 AF XY: 0.0000955 AC XY: 68 AN XY: 711672

African (AFR) AF: 0.0000302 AC: 1 AN: 33100

American (AMR) AF: 0.000235 AC: 10 AN: 42466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25708

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38890

South Asian (SAS) AF: 0.0000959 AC: 8 AN: 83382

European-Finnish (FIN) AF: 0.0000228 AC: 1 AN: 43824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5002

European-Non Finnish (NFE) AF: 0.0000835 AC: 92 AN: 1102222

Other (OTH) AF: 0.000219 AC: 13 AN: 59424

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151322 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73964

African (AFR) AF: 0.0000726 AC: 3 AN: 41342

American (AMR) AF: 0.000591 AC: 9 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5142

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

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

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67536

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs149021782; hg19: chr22-38161839;