22-37701731-T-A

Position:

• chr22-37701731-T-A

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.114+252T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,334 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (344 hom., cov: 32)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-37701731-T-A is Benign according to our data. Variant chr22-37701731-T-A is described in ClinVar as [Benign]. Clinvar id is 1178629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.114+252T>A		intron_variant		ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.114+252T>A		intron_variant			NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*450+252T>A		intron_variant		5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.250+252T>A		intron_variant		1
TRIOBP	ENST00000344404.10	n.114+252T>A		intron_variant		2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8939 AN: 152216 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0588 AC: 8964 AN: 152334 Hom.: 344 Cov.: 32 AF XY: 0.0585 AC XY: 4360 AN XY: 74504

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0510 Hom.: 26

Bravo AF: 0.0593

Asia WGS AF: 0.0430 AC: 149 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.41

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: rs73409450; hg19: chr22-38097738;