16-670293-G-A

Variant summary

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

The NM_138769.3(RHOT2):​c.374G>A​(p.Gly125Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,490 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: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RHOT2
NM_138769.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81
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]

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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=0.21220389).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RHOT2NM_138769.3 linkc.374G>A p.Gly125Glu missense_variant 7/19 ENST00000315082.9 NP_620124.1 Q8IXI1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHOT2ENST00000315082.9 linkc.374G>A p.Gly125Glu missense_variant 7/191 NM_138769.3 ENSP00000321971.4 Q8IXI1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460490
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
726520
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsDec 14, 2021The c.374G>A (p.G125E) alteration is located in exon 7 (coding exon 7) of the RHOT2 gene. This alteration results from a G to A substitution at nucleotide position 374, causing the glycine (G) at amino acid position 125 to be replaced by a glutamic acid (E). 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
0.12
BayesDel_addAF
Uncertain
0.086
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Benign
0.76
DEOGEN2
Benign
0.11
T;.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.043
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
-0.025
N;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.5
N;.;.
REVEL
Uncertain
0.33
Sift
Benign
1.0
T;.;.
Sift4G
Benign
0.77
T;T;T
Polyphen
0.36
B;.;.
Vest4
0.62
MutPred
0.33
Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);.;
MVP
0.83
MPC
0.22
ClinPred
0.63
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.59

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.

Other links and lift over

dbSNP: rs2038698328; hg19: chr16-720293; API