chr16-669593-C-G

Variant names:

• chr16-669593-C-G
• rs142141341
• NM_138769.3:c.263C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138769.3(RHOT2):​c.263C>G​(p.Ala88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RHOT2 NM_138769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

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

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=0.13844305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOT2	NM_138769.3	c.263C>G	p.Ala88Gly	missense_variant	Exon 5 of 19	ENST00000315082.9	NP_620124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOT2	ENST00000315082.9	c.263C>G	p.Ala88Gly	missense_variant	Exon 5 of 19	1	NM_138769.3	ENSP00000321971.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.48	N;.
REVEL	Benign	0.080
Sift	Benign	0.28	T;.
Sift4G	Benign	0.26	T;T
Polyphen		0.15	B;.
Vest4		0.39
MutPred		0.36		Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.77
MPC		0.11
ClinPred		0.35	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs142141341; hg19: chr16-719593;