17-32206951-A-G

Variant names:

• chr17-32206951-A-G
• rs16967164
• NM_001033566.3:c.1458A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001033566.3(RHOT1):​c.1458A>G​(p.Glu486Glu) 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
• Publications: 24 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT1	NM_001033566.3	MANE Select	c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 20	NP_001028738.1
	RHOT1	NM_001033568.3		c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 21	NP_001028740.1
	RHOT1	NM_001288754.2		c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 20	NP_001275683.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT1	ENST00000545287.7	TSL:5 MANE Select	c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 20	ENSP00000439737.2
	RHOT1	ENST00000358365.7	TSL:1	c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 21	ENSP00000351132.3
	RHOT1	ENST00000333942.10	TSL:1	c.1458A>G	p.Glu486Glu	synonymous	Exon 17 of 19	ENSP00000334724.6

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

GnomAD2 exomes AF: 0.224 AC: 55863 AN: 249554 AF XY: 0.218

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 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

African (AFR) AF: 0.525 AC: 17338 AN: 33026

American (AMR) AF: 0.255 AC: 11263 AN: 44238

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5423 AN: 25992

East Asian (EAS) AF: 0.222 AC: 8772 AN: 39532

South Asian (SAS) AF: 0.272 AC: 23199 AN: 85328

European-Finnish (FIN) AF: 0.150 AC: 8025 AN: 53338

Middle Eastern (MID) AF: 0.250 AC: 1435 AN: 5750

European-Non Finnish (NFE) AF: 0.174 AC: 192241 AN: 1104032

Other (OTH) AF: 0.211 AC: 12648 AN: 60006

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

African (AFR) AF: 0.510 AC: 21127 AN: 41432

American (AMR) AF: 0.220 AC: 3360 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5176

South Asian (SAS) AF: 0.269 AC: 1298 AN: 4818

European-Finnish (FIN) AF: 0.147 AC: 1553 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12014 AN: 67988

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.211 Hom.: 5410

Bravo AF: 0.290

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.9
DANN	Benign	0.92
PhyloP100		0.88
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=72/28	polymorphism

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