chr22-37765828-T-TGGG

Position:

• chr22-37765828-T-TGGG

Variant summary

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

The NM_001039141.3(TRIOBP):​c.6472+17_6472+19dupGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,401,624 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.6472+17_6472+19dupGGG		intron_variant		ENST00000644935.1	NP_001034230.1
TRIOBP	NM_007032.5	c.1333+17_1333+19dupGGG		intron_variant			NP_008963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+17_6472+19dupGGG		intron_variant			NM_001039141.3	ENSP00000496394.1
TRIOBP	ENST00000403663.6	c.1333+17_1333+19dupGGG		intron_variant		1		ENSP00000386026.2
TRIOBP	ENST00000344404.10	n.*5955+17_*5955+19dupGGG		intron_variant		2		ENSP00000340312.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1401624 Hom.: 0 Cov.: 34 AF XY: 0.00000432 AC XY: 3 AN XY: 694602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000992

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000724

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

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;