rs34538349

Variant names:

• chr17-32199495-G-GT
• rs34538349
• NM_001033566.3:c.1048dupT

Variant summary

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

The NM_001033566.3(RHOT1):​c.1048dupT​(p.Cys350LeufsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOT1 NM_001033566.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00
• Publications: 1 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 2 ACMG points.

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

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.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 of 20	NP_001028738.1	Q8IXI2-7
	RHOT1	NM_001033568.3		c.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 of 21	NP_001028740.1	Q8IXI2-3
	RHOT1	NM_001288754.2		c.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 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.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 of 20	ENSP00000439737.2	Q8IXI2-7
	RHOT1	ENST00000358365.7	TSL:1	c.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 of 21	ENSP00000351132.3	Q8IXI2-3
	RHOT1	ENST00000333942.10	TSL:1	c.1048dupT	p.Cys350LeufsTer4	frameshift	Exon 13 of 19	ENSP00000334724.6	Q8IXI2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

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

dbSNP: rs34538349;

hg19: chr17-30526514;