22-37765828-TGG-TGGGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_001039141.3(TRIOBP):c.6472+18_6472+19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000771 in 1,533,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00082 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 22-37765828-T-TGG is Benign according to our data. Variant chr22-37765828-T-TGG is described in ClinVar as [Benign]. Clinvar id is 1598921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000825 (1140/1382014) while in subpopulation SAS AF= 0.00197 (159/80524). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4_exome. There are 640 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.6472+18_6472+19dup		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.1333+18_1333+19dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+18_6472+19dup		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000403663.6	c.1333+18_1333+19dup		intron_variant		1		P2
TRIOBP	ENST00000344404.10	c.*5955+18_*5955+19dup		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000278 AC: 42 AN: 151170 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00189

Gnomad FIN AF: 0.000572

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000266

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000825 AC: 1140 AN: 1382014 Hom.: 0 Cov.: 34 AF XY: 0.000934 AC XY: 640 AN XY: 685064

Gnomad4 AFR exome AF: 0.00154

Gnomad4 AMR exome AF: 0.000906

Gnomad4 ASJ exome AF: 0.000322

Gnomad4 EAS exome AF: 0.000832

Gnomad4 SAS exome AF: 0.00197

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.000669

Gnomad4 OTH exome AF: 0.000839

GnomAD4 genome AF: 0.000278 AC: 42 AN: 151288 Hom.: 0 Cov.: 0 AF XY: 0.000338 AC XY: 25 AN XY: 73856

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.000572

Gnomad4 NFE AF: 0.000266

Gnomad4 OTH AF: 0.00

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

Invitae

Dec 22, 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: rs3833924; hg19: chr22-38161835;