Variant 12-121779647-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000267205.7(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. 16/21 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
ENST00000267205.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042888135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOF	NM_019034.3 linkuse as main transcript	c.487G>A	p.Glu163Lys	missense_variant	5/5	ENST00000267205.7	NP_061907.2
TMEM120B	NM_001080825.2 linkuse as main transcript	c.*3925C>T		3_prime_UTR_variant	12/12	ENST00000449592.7	NP_001074294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOF	ENST00000267205.7 linkuse as main transcript	c.487G>A	p.Glu163Lys	missense_variant	5/5	1	NM_019034.3	ENSP00000267205	P1	Q9HBH0-1
TMEM120B	ENST00000449592.7 linkuse as main transcript	c.*3925C>T		3_prime_UTR_variant	12/12	1	NM_001080825.2	ENSP00000404991	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250612

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135566

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.487G>A (p.E163K) alteration is located in exon 5 (coding exon 5) of the RHOF gene. This alteration results from a G to A substitution at nucleotide position 487, causing the glutamic acid (E) at amino acid position 163 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.083

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.81

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.16

N;.;.

REVEL

Benign

0.19

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.010

B;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over