22-37710392-C-T

Position:

• chr22-37710392-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001039141.3(TRIOBP):​c.115-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,611,398 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (18 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.755

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-37710392-C-T is Benign according to our data. Variant chr22-37710392-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1215413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00378 (576/152344) while in subpopulation NFE AF= 0.00398 (271/68012). AF 95% confidence interval is 0.00359. There are 5 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.115-35C>T		intron_variant		ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.115-35C>T		intron_variant			NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*451-35C>T		intron_variant		5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.251-35C>T		intron_variant		1
TRIOBP	ENST00000344404.10	n.115-35C>T		intron_variant		2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 577 AN: 152226 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00354 AC: 866 AN: 244400 Hom.: 5 AF XY: 0.00356 AC XY: 474 AN XY: 133246

Gnomad AFR exome AF: 0.000457

Gnomad AMR exome AF: 0.00192

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.000167

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.00384

Gnomad OTH exome AF: 0.00467

GnomAD4 exome AF: 0.00361 AC: 5268 AN: 1459054 Hom.: 18 Cov.: 32 AF XY: 0.00354 AC XY: 2573 AN XY: 726014

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.00377

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152344 Hom.: 5 Cov.: 33 AF XY: 0.00439 AC XY: 327 AN XY: 74494

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.00398

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00233

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.84

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: rs145499943; hg19: chr22-38106399;