17-32208261-C-T

Variant names:

• chr17-32208261-C-T
• rs199545262
• NM_001033566.3:c.1691C>T

Variant summary

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

The NM_001033566.3(RHOT1):​c.1691C>T​(p.Ala564Val) 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. 13/21 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. A564G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOT1 NM_001033566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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]

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=0.13862151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOT1	NM_001033566.3	c.1691C>T	p.Ala564Val	missense_variant	Exon 18 of 20	ENST00000545287.7	NP_001028738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOT1	ENST00000545287.7	c.1691C>T	p.Ala564Val	missense_variant	Exon 18 of 20	5	NM_001033566.3	ENSP00000439737.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.093	T;.;.;T;.;.;T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M;.;M;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;N;.;.;.;N;.
REVEL	Benign	0.017
Sift	Benign	0.22	T;T;.;.;.;T;.
Sift4G	Benign	0.31	T;T;T;T;T;T;D
Polyphen		0.0050	B;B;.;.;.;B;.
Vest4		0.13
MutPred		0.26		Loss of ubiquitination at K567 (P = 0.0432);Loss of ubiquitination at K567 (P = 0.0432);Loss of ubiquitination at K567 (P = 0.0432);.;Loss of ubiquitination at K567 (P = 0.0432);Loss of ubiquitination at K567 (P = 0.0432);.;
MVP		0.51
MPC		0.57
ClinPred		0.39	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.41

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: rs199545262; hg19: chr17-30535280;