Variant chr16-668683-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138769.3(RHOT2):c.206G>A(p.Arg69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,603,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RHOT2
NM_138769.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.878

Variant links:

Genes affected

RHOT2 (HGNC:21169): (ras homolog family member T2) This gene encodes a member of the Rho family of GTPases. The encoded protein is localized to the outer mitochondrial membrane and plays a role in mitochondrial trafficking and fusion-fission dynamics. [provided by RefSeq, Nov 2011]

RHOT2 links:

RHOT2 (HGNC:):

RHOT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 (MetaRNN=0.06550592).

BP6

Variant 16-668683-G-A is Benign according to our data. Variant chr16-668683-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2366047.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOT2	NM_138769.3 linkuse as main transcript	c.206G>A	p.Arg69Gln	missense_variant	4/19	ENST00000315082.9	NP_620124.1	Q8IXI1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOT2	ENST00000315082.9 linkuse as main transcript	c.206G>A	p.Arg69Gln	missense_variant	4/19	1	NM_138769.3	ENSP00000321971.4		Q8IXI1-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000213

AC:

AN:

234650

Hom.:

AF XY:

0.00000779

AC XY:

AN XY:

128390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000309

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:

0.0000282

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1451670

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

722096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000252

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:

0.00000812

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.000118

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000715

Hom.:

Bravo

AF:

0.000355

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.20

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.040

N;.;.

REVEL

Benign

0.042

Sift

Benign

0.38

T;.;.

Sift4G

Benign

0.39

T;T;T

Polyphen

0.016

B;.;.

Vest4

0.28

MVP

0.77

MPC

0.13

ClinPred

0.083

GERP RS

1.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.041

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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