rs3743912

chr16-670960-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_138769.3(RHOT2):c.708C>T(p.Asn236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,569,832 control chromosomes in the GnomAD database, including 16,535 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 0.17 (2695 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13840 hom.)
• Consequence: RHOT2 NM_138769.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.429 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHOT2	NM_138769.3	c.708C>T	p.Asn236=	synonymous_variant	10/19	ENST00000315082.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHOT2	ENST00000315082.9	c.708C>T	p.Asn236=	synonymous_variant	10/19	1	NM_138769.3	P4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26420 AN: 152074 Hom.: 2687 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.161 AC: 34810 AN: 216822 Hom.: 3148 AF XY: 0.152 AC XY: 17779 AN XY: 117208

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.307

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.133 AC: 188867 AN: 1417640 Hom.: 13840 Cov.: 34 AF XY: 0.133 AC XY: 92812 AN XY: 700122

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0989

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.174 AC: 26463 AN: 152192 Hom.: 2695 Cov.: 33 AF XY: 0.173 AC XY: 12898 AN XY: 74406

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.157

Alfa AF: 0.145 Hom.: 718

Bravo AF: 0.181

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	1.1
Dann	Benign	0.89
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs3743912; hg19: chr16-720960; COSMIC: COSV53467935; COSMIC: COSV53467935;