22-37701177-G-C

Variant names:

• chr22-37701177-G-C
• rs116432556
• NM_001039141.3:c.-60-129G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001039141.3(TRIOBP):​c.-60-129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 581,916 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (1 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347
• 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

ENSG00000100101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-37701177-G-C is Benign according to our data. Variant chr22-37701177-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00633 (949/149818) while in subpopulation AFR AF = 0.0219 (901/41112). AF 95% confidence interval is 0.0207. There are 8 homozygotes in GnomAd4. There are 441 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3	c.-60-129G>C		intron_variant	Intron 2 of 23	ENST00000644935.1	NP_001034230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1	c.-60-129G>C		intron_variant	Intron 2 of 23		NM_001039141.3	ENSP00000496394.1
ENSG00000100101	ENST00000455236.4	n.*277-129G>C		intron_variant	Intron 8 of 12	5		ENSP00000477208.1
TRIOBP	ENST00000492485.5	n.77-129G>C		intron_variant	Intron 1 of 4	1
TRIOBP	ENST00000344404.10	n.-60-129G>C		intron_variant	Intron 1 of 21	2		ENSP00000340312.6

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 949 AN: 149700 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00227

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.0000446

Gnomad OTH AF: 0.00443

GnomAD4 exome AF: 0.000773 AC: 334 AN: 432098 Hom.: 1 AF XY: 0.000620 AC XY: 142 AN XY: 228906

African (AFR) AF: 0.0196 AC: 251 AN: 12802

American (AMR) AF: 0.00135 AC: 33 AN: 24500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13988

East Asian (EAS) AF: 0.00 AC: 0 AN: 27760

South Asian (SAS) AF: 0.0000202 AC: 1 AN: 49540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26498

Middle Eastern (MID) AF: 0.00106 AC: 2 AN: 1888

European-Non Finnish (NFE) AF: 0.0000199 AC: 5 AN: 250662

Other (OTH) AF: 0.00172 AC: 42 AN: 24460

GnomAD4 genome AF: 0.00633 AC: 949 AN: 149818 Hom.: 8 Cov.: 32 AF XY: 0.00604 AC XY: 441 AN XY: 73042

African (AFR) AF: 0.0219 AC: 901 AN: 41112

American (AMR) AF: 0.00227 AC: 34 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10200

Middle Eastern (MID) AF: 0.00699 AC: 2 AN: 286

European-Non Finnish (NFE) AF: 0.0000446 AC: 3 AN: 67218

Other (OTH) AF: 0.00438 AC: 9 AN: 2054

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.00685

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs116432556; hg19: chr22-38097184;