rs9902253

Variant names:

• chr17-32222354-A-G
• rs9902253
• NM_001033566.3:c.1863-2262A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RHOT1	NM_001033566.3	c.1863-2262A>G		intron_variant	Intron 19 of 19	ENST00000545287.7	NP_001028738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOT1	ENST00000545287.7	c.1863-2262A>G		intron_variant	Intron 19 of 19	5	NM_001033566.3	ENSP00000439737.2

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

African (AFR) AF: 0.183 AC: 7598 AN: 41494

American (AMR) AF: 0.185 AC: 2832 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5170

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11906 AN: 67996

Other (OTH) AF: 0.183 AC: 386 AN: 2114

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
PhyloP100		0.079
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9902253; hg19: chr17-30549373;