rs78758968

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039141.3(TRIOBP):c.6272G>A(p.Ser2091Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2091T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03193441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRIOBP	NM_001039141.3 linkuse as main transcript	c.6272G>A	p.Ser2091Asn	missense_variant	17/24	ENST00000644935.1
TRIOBP	NM_007032.5 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	7/14
TRIOBP	NM_138632.2 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.6272G>A	p.Ser2091Asn	missense_variant	17/24		NM_001039141.3	A2	Q9H2D6-1
TRIOBP	ENST00000403663.6 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	7/14	1		P2	Q9H2D6-7
TRIOBP	ENST00000407319.7 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	7/8	1			Q9H2D6-6
TRIOBP	ENST00000344404.10 linkuse as main transcript	c.*5755G>A		3_prime_UTR_variant, NMD_transcript_variant	15/22	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

248942

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460860

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.77

Cadd

Benign

4.2

Dann

Benign

0.75

DEOGEN2

Benign

0.012

T;T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

M_CAP

Benign

0.0076

MetaRNN

Benign

0.032

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.41

N;N;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.34

N;.;N;N;.

REVEL

Benign

0.055

Sift

Benign

0.92

T;.;T;T;.

Sift4G

Benign

0.60

T;.;T;T;.

Polyphen

0.0010

B;B;.;.;.

Vest4

0.075

MutPred

0.13

Loss of glycosylation at S2091 (P = 0.0296);Loss of glycosylation at S2091 (P = 0.0296);.;.;.;

MVP

0.22

MPC

0.11

ClinPred

0.023

GERP RS

0.0092

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.17

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

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