22-37765831-G-C

Variant names:

• chr22-37765831-G-C
• rs45503898
• NM_001039141.3:c.6472+14G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001039141.3(TRIOBP):​c.6472+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,586,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.772
• Publications: 0 publications found

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]

TRIOBP Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 22-37765831-G-C is Benign according to our data. Variant chr22-37765831-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1632594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00035 (53/151444) while in subpopulation AFR AF = 0.00114 (47/41160). AF 95% confidence interval is 0.000882. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6472+14G>C		intron	N/A	NP_001034230.1
	TRIOBP	NM_007032.5		c.1333+14G>C		intron	N/A	NP_008963.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.6472+14G>C		intron	N/A	ENSP00000496394.1
	TRIOBP	ENST00000403663.6	TSL:1	c.1333+14G>C		intron	N/A	ENSP00000386026.2
	TRIOBP	ENST00000344404.10	TSL:2	n.*5955+14G>C		intron	N/A	ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.000344 AC: 52 AN: 151328 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000590

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000108 AC: 22 AN: 202864 AF XY: 0.0000802

Gnomad AFR exome AF: 0.000872

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000554

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 169 AN: 1434600 Hom.: 0 Cov.: 34 AF XY: 0.000115 AC XY: 82 AN XY: 711960

African (AFR) AF: 0.000726 AC: 24 AN: 33060

American (AMR) AF: 0.000118 AC: 5 AN: 42482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.000129 AC: 5 AN: 38872

South Asian (SAS) AF: 0.0000240 AC: 2 AN: 83476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5014

European-Non Finnish (NFE) AF: 0.000112 AC: 123 AN: 1102632

Other (OTH) AF: 0.000168 AC: 10 AN: 59444

GnomAD4 genome AF: 0.000350 AC: 53 AN: 151444 Hom.: 0 Cov.: 32 AF XY: 0.000338 AC XY: 25 AN XY: 74038

African (AFR) AF: 0.00114 AC: 47 AN: 41160

American (AMR) AF: 0.000132 AC: 2 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000590 AC: 4 AN: 67774

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000357 Hom.: 1

Bravo AF: 0.000431

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-0.77
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

Other links and lift over

dbSNP: rs45503898; hg19: chr22-38161838;