chr22-37765832-G-GT

Position:

• chr22-37765832-G-GT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001039141.3(TRIOBP):​c.6472+15_6472+16insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000908 in 1,585,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-37765832-G-GT is Benign according to our data. Variant chr22-37765832-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 2955208.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.6472+15_6472+16insT		intron_variant		ENST00000644935.1	NP_001034230.1
TRIOBP	NM_007032.5	c.1333+15_1333+16insT		intron_variant			NP_008963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+15_6472+16insT		intron_variant			NM_001039141.3	ENSP00000496394	A2
TRIOBP	ENST00000403663.6	c.1333+15_1333+16insT		intron_variant		1		ENSP00000386026	P2
TRIOBP	ENST00000344404.10	c.*5955+15_*5955+16insT		intron_variant, NMD_transcript_variant		2		ENSP00000340312

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.0000642 AC: 13 AN: 202474 Hom.: 0 AF XY: 0.0000536 AC XY: 6 AN XY: 111982

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000629

Gnomad SAS exome AF: 0.0000737

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000555

Gnomad OTH exome AF: 0.000193

GnomAD4 exome AF: 0.0000879 AC: 126 AN: 1434018 Hom.: 0 Cov.: 35 AF XY: 0.0000955 AC XY: 68 AN XY: 711672

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.000235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.0000959

Gnomad4 FIN exome AF: 0.0000228

Gnomad4 NFE exome AF: 0.0000835

Gnomad4 OTH exome AF: 0.000219

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151322 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73964

Gnomad4 AFR AF: 0.0000726

Gnomad4 AMR AF: 0.000591

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.000947

Bravo AF: 0.000125

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149021782; hg19: chr22-38161839;