22-37701198-T-TAA

Position:

• chr22-37701198-T-TAA

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000100101 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.-60-107_-60-106dupAA		intron_variant		ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.-60-107_-60-106dupAA		intron_variant			NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*277-107_*277-106dupAA		intron_variant		5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.77-107_77-106dupAA		intron_variant		1
TRIOBP	ENST00000344404.10	n.-60-107_-60-106dupAA		intron_variant		2		ENSP00000340312.6

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

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.279

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

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.262

Alfa AF: 0.268 Hom.: 646

Bravo AF: 0.238

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34316404; hg19: chr22-38097205;