rs16967164

Positions:

• chr17-32206951-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001033566.3(RHOT1):​c.1458A>G​(p.Glu486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,603,316 control chromosomes in the GnomAD database, including 37,813 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 0.28 (7485 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30328 hom.)
• Consequence: RHOT1 NM_001033566.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.875 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOT1	NM_001033566.3	c.1458A>G	p.Glu486=	synonymous_variant	17/20	ENST00000545287.7	NP_001028738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOT1	ENST00000545287.7	c.1458A>G	p.Glu486=	synonymous_variant	17/20	5	NM_001033566.3	ENSP00000439737	P3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41857 AN: 151956 Hom.: 7438 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.224 AC: 55863 AN: 249554 Hom.: 7398 AF XY: 0.218 AC XY: 29456 AN XY: 134854

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.193 AC: 280344 AN: 1451242 Hom.: 30328 Cov.: 28 AF XY: 0.195 AC XY: 140547 AN XY: 722332

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.276 AC: 41958 AN: 152074 Hom.: 7485 Cov.: 32 AF XY: 0.273 AC XY: 20279 AN XY: 74358

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.248

Alfa AF: 0.209 Hom.: 4711

Bravo AF: 0.290

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.9
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs16967164; hg19: chr17-30533970; COSMIC: COSV61714587; COSMIC: COSV61714587;