16-668660-C-T

Variant names:

• chr16-668660-C-T
• rs1370170734
• NM_138769.3:c.183C>T
• RHOT2 p.Ala61Ala

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001352280.2(RHOT2):​c.-122C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,936 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RHOT2 NM_001352280.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.38
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352280.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT2	NM_138769.3	MANE Select	c.183C>T	p.Ala61Ala	synonymous	Exon 4 of 19	NP_620124.1	Q8IXI1-1
	RHOT2	NM_001352280.2		c.-122C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 19	NP_001339209.1
	RHOT2	NM_001352281.2		c.-122C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 19	NP_001339210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT2	ENST00000315082.9	TSL:1 MANE Select	c.183C>T	p.Ala61Ala	synonymous	Exon 4 of 19	ENSP00000321971.4	Q8IXI1-1
	RHOT2	ENST00000697194.1		c.183C>T	p.Ala61Ala	synonymous	Exon 4 of 19	ENSP00000513180.1	A0A8V8TM48
	RHOT2	ENST00000958324.1		c.183C>T	p.Ala61Ala	synonymous	Exon 4 of 19	ENSP00000628383.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453936 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 723338

African (AFR) AF: 0.00 AC: 0 AN: 32882

American (AMR) AF: 0.00 AC: 0 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39036

South Asian (SAS) AF: 0.00 AC: 0 AN: 85250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109276

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.6
DANN	Benign	0.96
PhyloP100		-7.4
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1370170734;

hg19: chr16-718660;