22-37710353-G-A

Position:

• chr22-37710353-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001039141.3(TRIOBP):​c.115-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,599,626 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (26 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.590

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=-0.61).
• BP6: Variant 22-37710353-G-A is Benign according to our data. Variant chr22-37710353-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00817 (1245/152332) while in subpopulation AFR AF= 0.0282 (1173/41580). AF 95% confidence interval is 0.0269. There are 17 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.115-74G>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.115-74G>A		intron_variant			NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*451-74G>A		intron_variant		5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.251-74G>A		intron_variant		1
TRIOBP	ENST00000344404.10	n.115-74G>A		intron_variant		2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.00803 AC: 1222 AN: 152214 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000948 AC: 1372 AN: 1447294 Hom.: 26 AF XY: 0.000880 AC XY: 634 AN XY: 720228

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.00308

GnomAD4 genome AF: 0.00817 AC: 1245 AN: 152332 Hom.: 17 Cov.: 33 AF XY: 0.00783 AC XY: 583 AN XY: 74480

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.00300

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00535 Hom.: 1

Bravo AF: 0.00893

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.82

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: rs115587759; hg19: chr22-38106360;