rs9902253

Positions:

• chr17-32222354-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033566.3(RHOT1):​c.1863-2262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,142 control chromosomes in the GnomAD database, including 2,598 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2598 hom., cov: 32)
• Consequence: RHOT1 NM_001033566.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOT1	NM_001033566.3	c.1863-2262A>G		intron_variant		ENST00000545287.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOT1	ENST00000545287.7	c.1863-2262A>G		intron_variant		5	NM_001033566.3	P3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27629 AN: 152024 Hom.: 2591 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27659 AN: 152142 Hom.: 2598 Cov.: 32 AF XY: 0.182 AC XY: 13502 AN XY: 74374

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.183

Alfa AF: 0.186 Hom.: 462

Bravo AF: 0.184

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs9902253; hg19: chr17-30549373;