rs1139897

Variant names:

• chr16-670986-G-A
• rs1139897
• NM_138769.3:c.734G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-670986-G-A
• chr16-670986-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138769.3(RHOT2):​c.734G>A​(p.Arg245Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,578,344 control chromosomes in the GnomAD database, including 60,553 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R245G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (5305 hom., cov: 32)
  • Exomes 𝑓: 0.26 (55248 hom.)
• Consequence: RHOT2 NM_138769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 49 publications found

Genes affected

RHOT2 (HGNC:21169): (ras homolog family member T2) This gene encodes a member of the Rho family of GTPases. The encoded protein is localized to the outer mitochondrial membrane and plays a role in mitochondrial trafficking and fusion-fission dynamics. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.0537154E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOT2	NM_138769.3	c.734G>A	p.Arg245Gln	missense_variant	Exon 10 of 19	ENST00000315082.9	NP_620124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOT2	ENST00000315082.9	c.734G>A	p.Arg245Gln	missense_variant	Exon 10 of 19	1	NM_138769.3	ENSP00000321971.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34107 AN: 151990 Hom.: 5301 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.329 AC: 72526 AN: 220382 AF XY: 0.327

Gnomad AFR exome AF: 0.0632

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.277

GnomAD4 exome AF: 0.258 AC: 368530 AN: 1426236 Hom.: 55248 Cov.: 35 AF XY: 0.262 AC XY: 185041 AN XY: 706218

African (AFR) AF: 0.0577 AC: 1900 AN: 32952

American (AMR) AF: 0.465 AC: 19783 AN: 42560

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5538 AN: 24186

East Asian (EAS) AF: 0.684 AC: 26894 AN: 39332

South Asian (SAS) AF: 0.408 AC: 33749 AN: 82730

European-Finnish (FIN) AF: 0.356 AC: 16138 AN: 45360

Middle Eastern (MID) AF: 0.199 AC: 1116 AN: 5610

European-Non Finnish (NFE) AF: 0.227 AC: 247993 AN: 1094494

Other (OTH) AF: 0.261 AC: 15419 AN: 59012

GnomAD4 genome AF: 0.224 AC: 34123 AN: 152108 Hom.: 5305 Cov.: 32 AF XY: 0.237 AC XY: 17607 AN XY: 74346

African (AFR) AF: 0.0683 AC: 2838 AN: 41524

American (AMR) AF: 0.341 AC: 5209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3620 AN: 5152

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3676 AN: 10606

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

European-Non Finnish (NFE) AF: 0.226 AC: 15371 AN: 67936

Other (OTH) AF: 0.219 AC: 462 AN: 2112

Alfa AF: 0.225 Hom.: 8494

Bravo AF: 0.214

TwinsUK AF: 0.229 AC: 849

ALSPAC AF: 0.217 AC: 837

ESP6500AA AF: 0.0673 AC: 294

ESP6500EA AF: 0.224 AC: 1920

ExAC AF: 0.309 AC: 37062

Asia WGS AF: 0.497 AC: 1723 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;T
MetaRNN	Benign	0.000031	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
PhyloP100		3.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.24	N;.
REVEL	Benign	0.056
Sift	Benign	0.056	T;.
Sift4G	Benign	0.080	T;D
Polyphen		0.027	B;.
Vest4		0.052
MPC		0.13
ClinPred		0.019	T
GERP RS		2.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Varity_R		0.081
gMVP		0.62
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: rs1139897; hg19: chr16-720986; COSMIC: COSV53466230; COSMIC: COSV53466230;