NM_138769.3:c.257A>T

Variant names:

• chr16-669587-A-T
• NM_138769.3:c.257A>T
• RHOT2 p.Glu86Val

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138769.3(RHOT2):​c.257A>T​(p.Glu86Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RHOT2 NM_138769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138769.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT2	NM_138769.3	MANE Select	c.257A>T	p.Glu86Val	missense	Exon 5 of 19	NP_620124.1	Q8IXI1-1
	RHOT2	NM_001352275.2		c.257A>T	p.Glu86Val	missense	Exon 5 of 19	NP_001339204.1	A0A8V8TM48
	RHOT2	NM_001352278.2		c.257A>T	p.Glu86Val	missense	Exon 5 of 18	NP_001339207.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT2	ENST00000315082.9	TSL:1 MANE Select	c.257A>T	p.Glu86Val	missense	Exon 5 of 19	ENSP00000321971.4	Q8IXI1-1
	RHOT2	ENST00000697194.1		c.257A>T	p.Glu86Val	missense	Exon 5 of 19	ENSP00000513180.1	A0A8V8TM48
	RHOT2	ENST00000958324.1		c.257A>T	p.Glu86Val	missense	Exon 5 of 19	ENSP00000628383.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.1
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.12	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.54

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-719587;