chr22-37759212-G-C

Position:

chr22-37759212-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001039141.3(TRIOBP):c.6272G>C(p.Ser2091Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,613,080 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 8 hom. )

Consequence

TRIOBP
NM_001039141.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003343314).

BP6

Variant 22-37759212-G-C is Benign according to our data. Variant chr22-37759212-G-C is described in ClinVar as [Benign]. Clinvar id is 43865.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 = 0.00397 (605/152220) while in subpopulation AFR AF= 0.0142 (588/41528). AF 95% confidence interval is 0.0132. There are 6 homozygotes in gnomad4. There are 302 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 linkuse as main transcript	c.6272G>C	p.Ser2091Thr	missense_variant	17/24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 linkuse as main transcript	c.1133G>C	p.Ser378Thr	missense_variant	7/14		NP_008963.3	Q9H2D6-7
TRIOBP	NM_138632.2 linkuse as main transcript	c.1133G>C	p.Ser378Thr	missense_variant	7/8		NP_619538.2	Q9H2D6-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.6272G>C	p.Ser2091Thr	missense_variant	17/24		NM_001039141.3	ENSP00000496394.1		Q9H2D6-1

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

603

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000884

AC:

220

AN:

248942

Hom.:

AF XY:

0.000658

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.000492

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:

0.000820

GnomAD4 exome

AF:

0.000439

AC:

642

AN:

1460860

Hom.:

Cov.:

AF XY:

0.000383

AC XY:

278

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.000626

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:

0.0000333

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.00397

AC:

605

AN:

152220

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000858

Hom.:

Bravo

AF:

0.00460

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00108

AC:

131

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

Ser2091Thr in Exon 17 of TRIOBP: This variant is not expected to have clinical s ignificance because it has been identified in 1.3% (50/3732) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs78758968). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.8

DANN

Benign

0.90

DEOGEN2

Benign

0.040

T;T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.66

.;T;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.76

N;N;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.67

N;.;N;N;.

REVEL

Benign

0.082

Sift

Benign

0.14

T;.;D;T;.

Sift4G

Benign

0.57

T;.;T;T;.

Polyphen

0.26

B;B;.;.;.

Vest4

0.22

MVP

0.23

MPC

0.14

ClinPred

0.0031

GERP RS

0.0092

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.20

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over