chr22-37710101-C-T

Variant names:

• chr22-37710101-C-T
• rs62236745
• NM_001039141.3:c.115-326C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039141.3(TRIOBP):​c.115-326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,280 control chromosomes in the GnomAD database, including 5,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5652 hom., cov: 36)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-37710101-C-T is Benign according to our data. Variant chr22-37710101-C-T is described in ClinVar as [Benign]. Clinvar id is 1243015.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.115-326C>T		intron_variant	Intron 3 of 23	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.115-326C>T		intron_variant	Intron 3 of 23		NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*451-326C>T		intron_variant	Intron 9 of 12	5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.251-326C>T		intron_variant	Intron 2 of 4	1
TRIOBP	ENST00000344404.10	n.115-326C>T		intron_variant	Intron 2 of 21	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37850 AN: 152162 Hom.: 5658 Cov.: 36

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37852 AN: 152280 Hom.: 5652 Cov.: 36 AF XY: 0.256 AC XY: 19026 AN XY: 74452

African (AFR) AF: 0.0751 AC: 3125 AN: 41586

American (AMR) AF: 0.295 AC: 4516 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1562 AN: 5172

South Asian (SAS) AF: 0.400 AC: 1936 AN: 4834

European-Finnish (FIN) AF: 0.361 AC: 3831 AN: 10610

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

European-Non Finnish (NFE) AF: 0.302 AC: 20559 AN: 68002

Other (OTH) AF: 0.275 AC: 581 AN: 2114

Alfa AF: 0.126 Hom.: 439

Bravo AF: 0.235

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.87
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs62236745; hg19: chr22-38106108;