rs376601715

chr22-37759273-G-Achr22-37759273-G-Cchr22-37759273-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039141.3(TRIOBP):c.6324+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,609,908 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 0.00019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-37759273-G-A is Benign according to our data. Variant chr22-37759273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165605.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-37759273-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.6324+9G>A		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.1185+9G>A		intron_variant
TRIOBP	NM_138632.2	c.1185+9G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.6324+9G>A		intron_variant			NM_001039141.3	A2
TRIOBP	ENST00000403663.6	c.1185+9G>A		intron_variant		1		P2
TRIOBP	ENST00000407319.7	c.1185+9G>A		intron_variant		1
TRIOBP	ENST00000344404.10	c.*5807+9G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000847 AC: 21 AN: 247942 Hom.: 0 AF XY: 0.0000889 AC XY: 12 AN XY: 134950

Gnomad AFR exome AF: 0.0000665

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000251 AC: 366 AN: 1457678 Hom.: 0 Cov.: 30 AF XY: 0.000245 AC XY: 178 AN XY: 725316

Gnomad4 AFR exome AF: 0.0000898

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000310

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152230 Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11 AN XY: 74438

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.000159

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 09, 2013

6324+9G>A in intron 17 of TRIOBP: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and it has been identified in 0.01% (1/8582) of European American chromosomes and 0. 02% (1/4388) of African American chromosomes by the NHLBI Exome Sequencing Proje ct (http://evs.gs.washington.edu/EVS/) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.53
Dann	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs376601715; hg19: chr22-38155280;