Genetic Variant NM_138769.3:c.708C>T (chr16-670960-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.429

Publications

15 publications found

Variant links:

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]

RHOT2 links:

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ACMG classification

Classification was made for transcript

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 link	c.708C>T	p.Asn236Asn	synonymous_variant	Exon 10 of 19	ENST00000315082.9	NP_620124.1	Q8IXI1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOT2	ENST00000315082.9 link	c.708C>T	p.Asn236Asn	synonymous_variant	Exon 10 of 19	1	NM_138769.3	ENSP00000321971.4		Q8IXI1-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26420

AN:

152074

Hom.:

2687

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.133

AC XY:

92812

AN XY:

700122

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9144

18288

27432

36576

45720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5080

10160

15240

20320

25400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26463

AN:

152192

Hom.:

2695

Cov.:

AF XY:

0.173

AC XY:

12898

AN XY:

74406

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8507

AN:

67988

Other (OTH)

AF:

0.157

AC:

331

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1111

2221

3332

4442

5553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over