16-670960-C-T

Variant names:

• chr16-670960-C-T
• rs3743912
• NM_138769.3:c.708C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_138769.3(RHOT2):​c.708C>T​(p.Asn236Asn) 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
• Publications: 15 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 -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 rank	MANE	Protein	UniProt
RHOT2	NM_138769.3	c.708C>T	p.Asn236Asn	synonymous_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.708C>T	p.Asn236Asn	synonymous_variant	Exon 10 of 19	1	NM_138769.3	ENSP00000321971.4

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

GnomAD2 exomes AF: 0.161 AC: 34810 AN: 216822 AF XY: 0.152

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 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

African (AFR) AF: 0.265 AC: 8644 AN: 32628

American (AMR) AF: 0.191 AC: 7984 AN: 41894

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 2321 AN: 23462

East Asian (EAS) AF: 0.308 AC: 12079 AN: 39224

South Asian (SAS) AF: 0.121 AC: 9826 AN: 80992

European-Finnish (FIN) AF: 0.143 AC: 6713 AN: 47048

Middle Eastern (MID) AF: 0.119 AC: 661 AN: 5534

European-Non Finnish (NFE) AF: 0.122 AC: 132626 AN: 1088324

Other (OTH) AF: 0.137 AC: 8013 AN: 58534

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

African (AFR) AF: 0.265 AC: 10989 AN: 41518

American (AMR) AF: 0.169 AC: 2589 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1463 AN: 5178

South Asian (SAS) AF: 0.118 AC: 568 AN: 4824

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8507 AN: 67988

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.147 Hom.: 876

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
PhyloP100		0.43
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
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: rs3743912; hg19: chr16-720960; COSMIC: COSV53467935; COSMIC: COSV53467935;