17-32194067-G-T

Variant names:

• chr17-32194067-G-T
• rs747003726
• NM_001033566.3:c.829G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001033566.3(RHOT1):​c.829G>T​(p.Asp277Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D277H) 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: 10.0
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033566.3. 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
	RHOT1	NM_001033566.3	MANE Select	c.829G>T	p.Asp277Tyr	missense	Exon 11 of 20	NP_001028738.1	Q8IXI2-7
	RHOT1	NM_001033568.3		c.829G>T	p.Asp277Tyr	missense	Exon 11 of 21	NP_001028740.1	Q8IXI2-3
	RHOT1	NM_001288754.2		c.829G>T	p.Asp277Tyr	missense	Exon 11 of 20	NP_001275683.1	Q8IXI2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT1	ENST00000545287.7	TSL:5 MANE Select	c.829G>T	p.Asp277Tyr	missense	Exon 11 of 20	ENSP00000439737.2	Q8IXI2-7
	RHOT1	ENST00000358365.7	TSL:1	c.829G>T	p.Asp277Tyr	missense	Exon 11 of 21	ENSP00000351132.3	Q8IXI2-3
	RHOT1	ENST00000333942.10	TSL:1	c.829G>T	p.Asp277Tyr	missense	Exon 11 of 19	ENSP00000334724.6	Q8IXI2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	32
DANN	Benign	0.95
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		10
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.61		Gain of helix (P = 0.062)
MVP		0.82
MPC		1.7
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.89

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

Other links and lift over

dbSNP: rs747003726; hg19: chr17-30521086;