NM_138769.3:c.708C>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138769.3(RHOT2):​c.708C>A​(p.Asn236Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RHOT2 NM_138769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOT2	NM_138769.3	c.708C>A	p.Asn236Lys	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.708C>A	p.Asn236Lys	missense_variant	Exon 10 of 19	1	NM_138769.3	ENSP00000321971.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417838 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 700232

African (AFR) AF: 0.00 AC: 0 AN: 32638

American (AMR) AF: 0.00 AC: 0 AN: 41924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23468

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 81012

European-Finnish (FIN) AF: 0.0000212 AC: 1 AN: 47090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088402

Other (OTH) AF: 0.00 AC: 0 AN: 58542

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.84
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		0.43
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.7	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D;.
Sift4G	Benign	0.18	T;T
Polyphen		0.95	P;.
Vest4		0.70
MutPred		0.48		Loss of helix (P = 0.0017);.;
MVP		0.68
MPC		0.21
ClinPred		0.99	D
GERP RS		-7.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.79
gMVP		0.64

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;