rs45503898

chr22-37765831-G-Achr22-37765831-G-Cchr22-37765831-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039141.3(TRIOBP):c.6472+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,586,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (1 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.6472+14G>A		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.1333+14G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6472+14G>A		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000403663.6	c.1333+14G>A		intron_variant		1		P2
TRIOBP	ENST00000344404.10	c.*5955+14G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000595 AC: 9 AN: 151328 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000493 AC: 10 AN: 202864 Hom.: 0 AF XY: 0.0000357 AC XY: 4 AN XY: 112200

Gnomad AFR exome AF: 0.000174

Gnomad AMR exome AF: 0.0000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000253

Gnomad SAS exome AF: 0.0000732

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000439 AC: 63 AN: 1434600 Hom.: 1 Cov.: 34 AF XY: 0.0000464 AC XY: 33 AN XY: 711960

Gnomad4 AFR exome AF: 0.0000907

Gnomad4 AMR exome AF: 0.0000706

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000360

Gnomad4 SAS exome AF: 0.000156

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000263

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome AF: 0.0000594 AC: 9 AN: 151444 Hom.: 0 Cov.: 32 AF XY: 0.0000675 AC XY: 5 AN XY: 74038

Gnomad4 AFR AF: 0.0000729

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.9
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45503898; hg19: chr22-38161838;