Variant 22-37768116-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039141.3(TRIOBP):c.6515G>T(p.Arg2172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.27

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25810918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 linkuse as main transcript	c.6515G>T	p.Arg2172Leu	missense_variant	19/24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 linkuse as main transcript	c.1376G>T	p.Arg459Leu	missense_variant	9/14		NP_008963.3	Q9H2D6-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.6515G>T	p.Arg2172Leu	missense_variant	19/24		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
TRIOBP	ENST00000403663.6 linkuse as main transcript	c.1376G>T	p.Arg459Leu	missense_variant	9/14	1		ENSP00000386026.2	Q9H2D6-7
TRIOBP	ENST00000344404.10 linkuse as main transcript	n.*5998G>T		non_coding_transcript_exon_variant	17/22	2		ENSP00000340312.6	H7BXW4
TRIOBP	ENST00000344404.10 linkuse as main transcript	n.*5998G>T		3_prime_UTR_variant	17/22	2		ENSP00000340312.6	H7BXW4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.067

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.7

D;.;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.0040

D;.;T

Polyphen

1.0

D;D;.

Vest4

0.69

MutPred

0.18

Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);.;

MVP

0.41

MPC

0.62

ClinPred

0.98

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over