22-37710101-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.115-326C>T		intron_variant		ENST00000644935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.115-326C>T		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000492485.5	n.251-326C>T		intron_variant, non_coding_transcript_variant		1
TRIOBP	ENST00000344404.10	c.115-326C>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.275

Alfa AF: 0.159 Hom.: 362

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs62236745; hg19: chr22-38106108;