12-121780906-C-T

Position:

chr12-121780906-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019034.3(RHOF):c.437G>A(p.Arg146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RHOF
NM_019034.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37

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:

TMEM120B (HGNC:):

TMEM120B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2470316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOF	NM_019034.3 linkuse as main transcript	c.437G>A	p.Arg146Gln	missense_variant	4/5	ENST00000267205.7	NP_061907.2	Q9HBH0-1
TMEM120B	NM_001080825.2 linkuse as main transcript	c.*5184C>T		3_prime_UTR_variant	12/12	ENST00000449592.7	NP_001074294.2	A0PK00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOF	ENST00000267205.7 linkuse as main transcript	c.437G>A	p.Arg146Gln	missense_variant	4/5	1	NM_019034.3	ENSP00000267205.2		Q9HBH0-1
TMEM120B	ENST00000449592.7 linkuse as main transcript	c.*5184C>T		3_prime_UTR_variant	12/12	1	NM_001080825.2	ENSP00000404991.2		A0PK00

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249070

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461482

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

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

Aug 09, 2021

The c.437G>A (p.R146Q) alteration is located in exon 4 (coding exon 4) of the RHOF gene. This alteration results from a G to A substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;D;D;.

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.82

L;.;.;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.11

T;.;.;.

Sift4G

Benign

0.32

T;T;.;T

Polyphen

0.99

D;.;.;D

Vest4

0.32

MutPred

0.41

Gain of catalytic residue at L150 (P = 0.0155);.;.;Gain of catalytic residue at L150 (P = 0.0155);

MVP

0.76

MPC

0.35

ClinPred

0.41

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.49

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