16-668359-T-G

Position:

• chr16-668359-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138769.3(RHOT2):​c.44T>G​(p.Val15Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RHOT2 NM_138769.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOT2	NM_138769.3	c.44T>G	p.Val15Gly	missense_variant	2/19	ENST00000315082.9	NP_620124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOT2	ENST00000315082.9	c.44T>G	p.Val15Gly	missense_variant	2/19	1	NM_138769.3	ENSP00000321971.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.44T>G (p.V15G) alteration is located in exon 2 (coding exon 2) of the RHOT2 gene. This alteration results from a T to G substitution at nucleotide position 44, causing the valine (V) at amino acid position 15 to be replaced by a glycine (G). 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D;.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Pathogenic	4.3	H;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.5	D;.;.
REVEL	Pathogenic	0.95
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.031	D;T;D
Polyphen		1.0	D;.;.
Vest4		0.59
MutPred		0.83		Loss of stability (P = 0.013);Loss of stability (P = 0.013);.;
MVP		0.90
MPC		0.61
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.96
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-718359;