rs369182277

Variant names:

• chr22-37765827-C-T
• rs369182277
• NM_001039141.3:c.6472+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37765827-C-T
• chr22-37765827-C-A
• chr22-37765827-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001039141.3(TRIOBP):​c.6472+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,509,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.371
• 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)
• hearing loss, autosomal recessive

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 22-37765827-C-T is Benign according to our data. Variant chr22-37765827-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00527 (399/75780) while in subpopulation AFR AF = 0.0299 (377/12596). AF 95% confidence interval is 0.0274. There are 0 homozygotes in GnomAd4. There are 193 alleles in the male GnomAd4 subpopulation. Median coverage is 27. 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	NM_001039141.3	MANE Select	c.6472+10C>T		intron	N/A	NP_001034230.1	Q9H2D6-1
	TRIOBP	NM_007032.5		c.1333+10C>T		intron	N/A	NP_008963.3	Q9H2D6-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIOBP	ENST00000644935.1	MANE Select	c.6472+10C>T		intron	N/A	ENSP00000496394.1	Q9H2D6-1
	TRIOBP	ENST00000403663.6	TSL:1	c.1333+10C>T		intron	N/A	ENSP00000386026.2	Q9H2D6-7
	TRIOBP	ENST00000344404.10	TSL:2	n.*5955+10C>T		intron	N/A	ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes AF: 0.00526 AC: 398 AN: 75718 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00219

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: 0.0000255

Gnomad OTH AF: 0.00273

GnomAD2 exomes AF: 0.00111 AC: 116 AN: 104946 AF XY: 0.000852

Gnomad AFR exome AF: 0.0340

Gnomad AMR exome AF: 0.000526

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000216

Gnomad OTH exome AF: 0.000343

GnomAD4 exome AF: 0.000279 AC: 400 AN: 1433416 Hom.: 1 Cov.: 31 AF XY: 0.000232 AC XY: 165 AN XY: 711330

African (AFR) AF: 0.0103 AC: 338 AN: 32958

American (AMR) AF: 0.000355 AC: 15 AN: 42276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 38676

South Asian (SAS) AF: 0.00 AC: 0 AN: 83360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4962

European-Non Finnish (NFE) AF: 0.00000726 AC: 8 AN: 1101320

Other (OTH) AF: 0.000657 AC: 39 AN: 59338

GnomAD4 genome AF: 0.00527 AC: 399 AN: 75780 Hom.: 0 Cov.: 27 AF XY: 0.00518 AC XY: 193 AN XY: 37230

African (AFR) AF: 0.0299 AC: 377 AN: 12596

American (AMR) AF: 0.00219 AC: 18 AN: 8236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2424

East Asian (EAS) AF: 0.00 AC: 0 AN: 2450

South Asian (SAS) AF: 0.00 AC: 0 AN: 2878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.0000255 AC: 1 AN: 39282

Other (OTH) AF: 0.00270 AC: 3 AN: 1110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00309

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs369182277; hg19: chr22-38161834;