Variant 17-32224729-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001033566.3(RHOT1):c.1976G>A(p.Arg659Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,592,378 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 Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

RHOT1
NM_001033566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33

Variant links:

Genes affected

RHOT1 (HGNC:21168): (ras homolog family member T1) Predicted to enable GTP binding activity and GTPase activity. Involved in cellular homeostasis; mitochondrial outer membrane permeabilization; and mitochondrion transport along microtubule. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHOT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3151269).

BS2

High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOT1	NM_001033566.3 linkuse as main transcript	c.1976G>A	p.Arg659Gln	missense_variant	20/20	ENST00000545287.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOT1	ENST00000545287.7 linkuse as main transcript	c.1976G>A	p.Arg659Gln	missense_variant	20/20	5	NM_001033566.3	P3	Q8IXI2-7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152108

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249892

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000972

AC:

AN:

1440270

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

716410

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000731

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.2072G>A (p.R691Q) alteration is located in exon 21 (coding exon 21) of the RHOT1 gene. This alteration results from a G to A substitution at nucleotide position 2072, causing the arginine (R) at amino acid position 691 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.21

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;.;T;.

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Uncertain

-0.0030

MutationAssessor

Uncertain

2.1

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

N;N;.;.;N

REVEL

Uncertain

0.46

Sift

Benign

0.14

T;D;.;.;T

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.81

P;D;.;.;P

Vest4

0.59

MutPred

0.34

Loss of MoRF binding (P = 0.018);.;.;.;.;

MVP

0.88

MPC

1.7

ClinPred

0.43

GERP RS

6.0

Varity_R

0.24

gMVP

0.32

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