Variant 22-37765831-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.772

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.6472+14G>C		intron_variant	Intron 18 of 23	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.1333+14G>C		intron_variant	Intron 8 of 13		NP_008963.3	Q9H2D6-7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000644935.1 link	c.6472+14G>C	intron_variant	Intron 18 of 23		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000403663.6 link	c.1333+14G>C	intron_variant	Intron 8 of 13	1		ENSP00000386026.2	Q9H2D6-7
TRIOBP	ENST00000344404.10 link	n.*5955+14G>C	intron_variant	Intron 16 of 21	2		ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.000344

AC:

AN:

151328

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000108

AC:

AN:

202864

Hom.:

AF XY:

0.0000802

AC XY:

AN XY:

112200

show subpopulations

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 SAS exome

AF:

0.0000732

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.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

711960

show subpopulations

Gnomad4 AFR exome

AF:

0.000726

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.000350

AC:

AN:

151444

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.00114

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000367

Hom.:

Bravo

AF:

0.000431

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over