17-32171097-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001033566.3(RHOT1):c.92A>G(p.Glu31Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOT1 NM_001033566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2964274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOT1	NM_001033566.3	c.92A>G	p.Glu31Gly	missense_variant	2/20	ENST00000545287.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOT1	ENST00000545287.7	c.92A>G	p.Glu31Gly	missense_variant	2/20	5	NM_001033566.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

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

Nov 22, 2023

The c.92A>G (p.E31G) alteration is located in exon 2 (coding exon 2) of the RHOT1 gene. This alteration results from a A to G substitution at nucleotide position 92, causing the glutamic acid (E) at amino acid position 31 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	Benign	0.22
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D;.;.;D;.;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.6	L;L;L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.7	D;D;D;.;.;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.013	D;D;T;.;.;D
Sift4G	Uncertain	0.034	D;T;D;D;D;T
Polyphen		0.064	B;B;.;.;.;B
Vest4		0.28
MutPred		0.38		Loss of disorder (P = 0.0947);Loss of disorder (P = 0.0947);Loss of disorder (P = 0.0947);.;Loss of disorder (P = 0.0947);Loss of disorder (P = 0.0947);
MVP		0.59
MPC		1.5
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.61
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-30498116;