Genetic Variant RHOF:p.Glu163Lys (chr12-121779647-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019034.3(RHOF):c.487G>A(p.Glu163Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RHOF
NM_019034.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

1 publications found

Variant links:

Genes affected

RHOF (HGNC:15703): (ras homolog family member F, filopodia associated) Predicted to enable GTP binding activity; GTPase activity; and protein kinase binding activity. Involved in actin filament organization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RHOF links:

TMEM120B (HGNC:32008): (transmembrane protein 120B) Predicted to be involved in fat cell differentiation and protein heterooligomerization. Predicted to be integral component of membrane. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM120B links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.042888135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019034.3. 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
	RHOF	NM_019034.3	MANE Select	c.487G>A	p.Glu163Lys	missense	Exon 5 of 5	NP_061907.2
	TMEM120B	NM_001080825.2	MANE Select	c.*3925C>T		3_prime_UTR	Exon 12 of 12	NP_001074294.2	A0PK00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHOF	ENST00000267205.7	TSL:1 MANE Select	c.487G>A	p.Glu163Lys	missense	Exon 5 of 5	ENSP00000267205.2	Q9HBH0-1
TMEM120B	ENST00000449592.7	TSL:1 MANE Select	c.*3925C>T		3_prime_UTR	Exon 12 of 12	ENSP00000404991.2	A0PK00
RHOF	ENST00000537265.5	TSL:2	c.187G>A	p.Glu63Lys	missense	Exon 4 of 4	ENSP00000476444.1	V9GY67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250612

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111876

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.083

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.68

M_CAP

Benign

0.017

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.81

PhyloP100

1.2

PrimateAI

Benign

0.41

PROVEAN

Benign

0.16

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.067

MutPred

0.47

Gain of catalytic residue at G158 (P = 0.0023)

MVP

0.57

MPC

0.29

ClinPred

0.067

GERP RS

-0.92

Varity_R

0.055

gMVP

0.45

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over